Dirofilaria and brugia ankyrin proteins, nucleic acid molecules, and uses thereof

ABSTRACT

The present invention relates to Dirofilaria ankyrin proteins and to Brugia ankyrin proteins; to Dirofilaria ankyrin nucleic acid molecules and to Brugia ankyrin nucleic acid molecules, including those that encode such ankyrin proteins; to antibodies raised against such ankyrin proteins; and to compounds that inhibit Dirofilaria or Brugia ankyrin function. The present invention also includes methods to identify and obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to protect animals from diseases caused by parasitic helminths.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 08/847,429, filed Apr. 24, 1997, now U.S. Pat. No. 5,827,692.The patent application referred to in this section is incorporated byreference herein in its entirety.

FIELD OF THE INVENTION

The present invention relates to Dirofilaria and Brugia ankyrin nucleicacid molecules, proteins encoded by such nucleic acid molecules,antibodies raised against such proteins, compounds capable of inhibitingthe function of such proteins and methods to identify such inhibitors.The present invention also includes therapeutic compositions comprisingsuch nucleic acid molecules, proteins, antibodies, and/or inhibitors, aswell as their use to protect animals from diseases caused by parasitichelminths, such as heartworm disease, elephantiasis, and hydrocele.

BACKGROUND OF THE INVENTION

Parasitic helminth infections in animals, including humans, aretypically treated by chemical drugs. One disadvantage with chemicaldrugs is that they must be administered often. For example, dogssusceptible to heartworm are typically treated monthly. Repeatedadministration of drugs, however, often leads to the development ofresistant helminth strains that no longer respond to treatment.Furthermore, many of the chemical drugs cause harmful side effects inthe animals being treated, and as larger doses become required due tothe build up of resistance, the side effects become even greater.Moreover, a number of drugs only treat symptoms of a parasitic diseasebut are unable to prevent infection by the parasitic helminth.

An alternative method to prevent parasitic helminth infection includesadministering a vaccine against a parasitic helminth. Although manyinvestigators have tried to develop vaccines based on specific antigens,it is well understood that the ability of an antigen to stimulateantibody production does not necessarily correlate with the ability ofthe antigen to stimulate an immune response capable of protecting ananimal from infection, particularly in the case of parasitic helminths.Although a number of prominent antigens have been identified in severalparasitic helminths, including in Dirofilaria and Brugia species, thereis yet to be a commercially available vaccine developed for anyparasitic helminth.

As an example of the complexity of parasitic helminths, the life cycleof D. immitis, the helminth that causes heartworm, includes a variety oflife forms, each of which presents different targets, and challenges,for immunization. In a mosquito, D. immitis microfilariae go through twolarval stages (L1 and L2) and become mature third stage larvae (L3),which can then be transmitted back to the dog when the mosquito takes ablood meal. In a dog, the L3 molt to the fourth larval stage (L4), andsubsequently to the fifth stage, or immature adults. The immature adultsmigrate to the heart and pulmonary arteries, where they mature to adultheartworms. Adult heartworms are quite large and preferentially inhabitthe heart and pulmonary arteries of an animal. Sexually mature adults,after mating, produce microfilariae which traverse capillary beds andcirculate in the vascular system of the dog. In particular, heartworm isa major problem in dogs, which typically do not develop immunity uponinfection (i.e., dogs can become reinfected even after being cured bychemotherapy). In addition, heartworm infection has been reported incats, ferrets, and humans.

As such, there remains a need to identify efficacious compositions thatprotect animals against diseases caused by parasitic helminths such asD. immitis and B. malayi. Such compositions would preferably alsoprotect animals from infection by such helminths.

The mechanisms and regulatory pathways involved in D. immitis migrationand development are not clear. From infective L3 to mature adult, thenematode has to migrate and develop, with two molts, within itsdefinitive host. It has been shown in the free living nematode,Caenorhabditis elegans (C. elegans), that the development of the larvaeis regulated by environmental signals through chemosensory neurons.Blockage of signal transmission affects the development of the nematode(Bargmann, et al., 1991, Science, 251, 1243-1246). Many neuron-relatedgenes have been identified in C. elegans. Mutations of the genes whichcontrol normal neuron function in C. elegans will not only affect thebehavior of the nematode, but will also affect the development of thelarvae and egg laying of mutated female worms. In parasitic nematodes,very little is known about mechanisms involved in the signaltransmission and the developmental regulation of the parasites. However,host and tissue specificities in parasite infections suggest thatparasitic nematodes might also need correct environmental signals fordevelopment.

Ankyrins are peripheral membrane proteins which have been found inerythrocyte, kidney and neuronal cells of mammals. Genes coding forthree different mammalian ankyrins (ankyrin_(R), ankyrin_(B) andankyrin_(G)) have been cloned. Ankyrin_(R) was originally identified aspart of the erythrocyte membrane skeleton, and was recently alsolocalized to the plasma membrane of a subpopulation of post mitoticneurons in rat brain (Lambert, et al., 1993, J. Neurosci., 13,3725-3735). Ankyrin_(B) is a developmentally regulated human brainprotein which has two alternatively spliced isoforms with molecularmasses of 220 kilodaltons (kD) and 440 kD (Kunimoto, et al., 1991, J.Cell Biology, 115, 1319-1331). Ankyrin_(G) is a more recently isolatedhuman gene that encodes two neural-specific ankyrin variants (480 kD and270 kD), which have been localized to the axonal initial segment andnode of Ranvier (Kordeli, et al., 1995, J. Biol. Chem., 270, 2352-2359).Studies on mammalian ankyrins indicate that ankyrins bind a variety ofproteins which have functions involved with the anion exchanger(Drenckhahn, et al., 1988, Science, 230, 1287-1289), Na+/K+-ATPase,amiloride-sensitive sodium channel in kidney (Smith, et al., 1991, Proc.Natl. Acad. Sci. U.S.A., 88, 6971-6975), voltage dependent sodiumchannel of the brain and the neuromuscularjunction (Srinivasan, et al.,1988, Nature, 333, 177-180), and nervous system cell adhesion molecules(Davis, et al., 1994, J. Biol. Chem., 269, 27163-27166).

Analyses of mammalian ankyrins have revealed that these large proteinsare divided into three functional domains. These include an N-terminalmembrane-binding domain of about 89-95 kD, a spectrin-binding domain ofabout 62 kD, and a C-terminal regulatory domain of about 50-55 kD. Themembrane-binding domain is primarily comprised of tandem repeats ofabout 33 amino acids each. This domain usually has about 22-24 copies ofthese repeats. The repeat units appear to function in binding tomembrane proteins such as anion exchangers, sodium channels, and certainadhesion molecules. The spectrin-binding domain, as the name implies,functions in binding to the spectrin-based cytoskeleton of cellspositioned inside the plasma membrane. Finally, the regulatory domain,which is the most variant domain among the different ankyrins that havebeen studied, appears to function in as a repressor and/or an activatorof the protein-binding activities of the other two domains. Some of thevariability seen in this domain among different ankyrin species appearsto be the result of alternative splicing of nascent transcripts. For areview of ankyrin structure and function, see, for example, Bennett,1992, J. Biol. Chem., 267, 8703-8706. Bennett, ibid., is hereinincorporated by reference in its entirety.

An ankyrin gene (UNC-44) has also been identified in the free livingnematode, C. elegans. Mutation of UNC-44 affects the development andfunction of the nervous system (Otsuka et al., 1995, J. Cell Biology,129, 1081-1092). More recently, a cDNA encoding a 90-kilodalton (kD)neuronal protein, E1, which is reported to be an ankyrin-relatedprotein, has been cloned from the filariid nematode, Onchocerca volvulus(O. volvulus), a human parasite. The cDNA was identified by usingimmuno-screening with antisera collected from putatively immuneindividuals from an endemic area of onchocerciasis. Localization studiesby immunohistochemical assay indicated that the O. volvulus E1 nativeprotein was localized to the nerve ring, the neuronal cell bodies, andthe basal labyrinth within the extracellular clefts of the hypodermis inthe adult nematode (Erttmann et al., 1996a, J. Biol. Chem., 271,1645-1650). This 462-amino acid O. volvulus protein is reported to befull length.

SUMMARY OF THE INVENTION

The present invention relates to a novel product and a process toprotect animals against parasitic helminth infection (e.g., preventand/or treat such an infection). According to the present inventionthere are provided Dirofilaria and Brugia ankyrin proteins and mimetopesthereof; Dirofilaria and Brugia ankyrin nucleic acid molecules,including those that encode such proteins; antibodies raised againstsuch ankyrin proteins (i.e., anti-Dirofilaria and anti-Brugia ankyrinantibodies); and compounds that inhibit the function of parasitichelminth ankyrins (i.e, inhibitory compounds).

The present invention also includes methods to obtain and/or identifysuch proteins, nucleic acid molecules, antibodies and inhibitorycompounds. Also included in the present invention are therapeuticcompositions comprising such proteins, nucleic acid molecules,antibodies, and/or inhibitory compounds, as well as use of suchtherapeutic compositions to protect animals from diseases caused byparasitic helminths.

One embodiment of the present invention is an isolated nucleic acidmolecule that includes either a Dirofilaria ankyrin nucleic acidmolecule, preferably a Dirofilaria immitis (D. immitis) ankyrin nucleicacid molecule, or a Brugia ankyrin nucleic acid molecule, preferably aBrugia malayi (B. malayi) ankyrin nucleic acid molecule. Such nucleicacid molecules are referred to as ankyrin nucleic acid molecules. A D.immitis ankyrin nucleic acid molecule preferably includes nucleic acidsequence SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:13, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ IDNO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ IDNO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:86, SEQ IDNO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ IDNO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ IDNO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ IDNO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQID NO:107, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114,SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ IDNO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQID NO:134, SEQ ID NO:136; SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:141,SEQ ID NO:143, SEQ ID NO:144, and/or SEQ ID NO:146, and a B. malayiankyrin nucleic acid molecule preferably includes nucleic acid sequenceSEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:40, and/or SEQ ID NO:41.

In one embodiment, a preferred D. immitis or B. malayi ankyrin nucleicacid molecule comprises a coding region of at least about 1500nucleotides, preferably at least about 3000 nucleotides, even morepreferably at least about 4500 nucleotides, which is capable of encodingan ankyrin protein of at least about 500 amino acids in length,preferably at least about 1000 amino acids in length, even morepreferably at least about 1500 amino acids in length. In anotherembodiment, a preferred D. immitis or B. malayi ankyrin nucleic acidmolecule comprises a full-length coding region which encodes afull-length ankyrin protein.

The present invention also relates to recombinant molecules, recombinantviruses and recombinant cells that include an isolated ankyrin nucleicacid molecule of the present invention. Also included are methods toproduce such nucleic acid molecules, recombinant molecules, recombinantviruses and recombinant cells.

Another embodiment of the present invention includes either aDirofilaria or a Brugia ankyrin protein, or a protein that includes aDirofilaria or a Brugia ankyrin protein. Preferred ankyrin proteinsinclude D. immitis ankyrin proteins or B. malayi ankyrin proteins. Apreferred D. immitis ankyrin protein comprises amino acid sequence SEQID NO:2, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:15, SEQ ID NO:20, SEQ IDNO:23, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:139, SEQ ID NO:142, SEQ IDNO:145, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:165, SEQID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170,and/or SEQ ID NO:171, and a preferred B. malayi ankyrin proteincomprises amino acid sequence SEQ ID NO:38.

In one embodiment, a preferred D. immitis or B. malayi ankyrin proteincomprises an amino acid sequence of at least about in length, preferablyat least about 1000 amino acids in length, even more preferably at leastabout 1500 amino acids in length. In another embodiment, a preferred D.immitis or B. malayi ankyrin protein comprises a full-length protein,i.e., a protein encoded by a full-length coding region.

The present invention also relates to: mimetopes of either Dirofilariaor Brugia ankyrin proteins, preferably to mimetopes of either D. immitisand B. malayi ankyrin proteins; isolated antibodies that selectivelybind to either Dirofilaria or Brugia ankyrin proteins or mimetopesthereof; and inhibitors of Dirofilaria or Brugia ankyrin proteinfunction. Also included are methods, including recombinant methods, toproduce proteins, mimetopes, antibodies, and inhibitors of the presentinvention.

Yet another embodiment of the present invention is a therapeuticcomposition that is capable of protecting an animal from disease causedby a parasitic helminth. Such a therapeutic composition includes one ormore of the following protective compounds: a Dirofilaria or a Brugiaankyrin protein or a mimetope thereof; an isolated Dirofilaria or Brugiaankyrin nucleic acid molecule; an isolated antibody that selectivelybinds to a Dirofilaria or a Brugia ankyrin protein; and/or a compoundcapable of inhibiting ankyrin function identified by its ability toinhibit either Dirofilaria or a Brugia ankyrin function. A preferredtherapeutic composition of the present invention also includes anexcipient, an adjuvant and/or a carrier. Preferred ankyrin nucleic acidmolecule therapeutic compositions of the present invention includegenetic vaccines, recombinant virus vaccines and recombinant cellvaccines. Also included in the present invention is a method to protectan animal from disease caused by a parasitic helminth, comprising thestep of administering to the animal a therapeutic composition of thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides for isolated Dirofilaria and Brugiaankyrin proteins, isolated Dirofilaria and Brugia ankyrin nucleic acidmolecules, antibodies directed against Dirofilaria and Brugia ankyrinproteins, and compounds able to inhibit parasitic helminth ankyrinfunction (i.e., inhibitory compounds). As used herein, the termsisolated Dirofilaria ankyrin proteins, isolated Brugia ankyrin proteins,isolated Dirofilaria ankyrin nucleic acid molecules, and isolated Brugiaankyrin nucleic acid molecules refers to ankyrin proteins and ankyrinnucleic acid molecules derived from parasitic helminths of the generaDirofilaria and Brugia and, as such, can be obtained from their naturalsource, or can be produced using, for example, recombinant nucleic acidtechnology or chemical synthesis. Also included in the present inventionis the use of these proteins, nucleic acid molecules, antibodies, andinhibitory compounds as therapeutic compositions to protect animals fromparasitic helminth diseases as well as in other applications, such asthose disclosed below.

The biological functions of ankyrin-related proteins in filariidnematodes are not known. However, inhibiting normal functions of thenervous system in parasitic nematodes might cause neurons to becomeinsensitive to exogenous signals and lead to defects in the developmentof the parasite. While not being bound by theory, the possible linkbetween neuronal proteins and the development of parasitic nematodesindicates that neuronal proteins, such as ankyrins, could be potentialcandidates for the development of a vaccine against parasitic nematodeinfections.

Dirofilaria and Brugia ankyrin proteins and nucleic acid molecules ofthe present invention have utility because they represent novel targetsfor anti-parasite vaccines and drugs. The products and processes of thepresent invention are advantageous because they enable the inhibition ofparasite developmental and migratory pathways that involve ankyrin.While not being bound by theory, it is believed that nematodeankyrin-like proteins might affect the development and function of thenematode nervous system, rendering neurons insensitive to exogenoussignals involved in migration and development.

Isolation of D. immitis and B. malayi ankyrin nucleic acid molecules andproteins of the present invention was surprising even in view of thereported O. volvulus E1 nucleic acid molecule and protein disclosed byErttmann, et al., 1996a, ibid., and the reported C. elegans UNC-44nucleic acid molecule and protein disclosed by Otsuka, et al., ibid. Asdescribed in more detail in the Examples, it was very difficult toisolate D. immitis ankyrin nucleic acid molecules, despite the knowledgeof these reported O. volvulus and C. elegans nucleic acid sequences.Moreover, Erttmann, et al., 1996b, Trop. Med. Int. Health, 1, 558-574,teaches away from a D. immitis analog of the O. volvulus E1 protein, inthat the reference discloses that affinity-purified rabbit antibodiesraised against the O. volvulus E1 protein do not react with D. immitisby immunohistochemical analysis (see Erttmann, et al., 1996b, ibid.,Table 2).

Furthermore, isolated D. immitis and B. malayi ankyrin nucleic acidmolecules and proteins of the present invention, and particularly D.immitis and B. malayi ankyrin nucleic acid molecules containingfull-length coding regions and full-length D. immitis and B. malayiankyrin proteins, are distinct from the O. volvulus E1 nucleic acidmolecule and protein disclosed by Erttmann, et al., 1996a, ibid. Forexample, the inventors disclose herein a D. immitis ankyrin cDNAmolecule of about 5503 nucleotides that encodes a full-length protein ofabout 1745 amino acids, and has a predicted size of about 191.7 kD. Thisnucleic acid molecule and protein are in dramatic contrast to thereported O. volvulus full-length E1 protein of 462 amino acids (the O.volvulus full-length E1 protein is only about 26% the size of the D.immitis full-length protein), and to the reported O. volvulus E1full-length cDNA molecule of 2043 nucleotides encoding that protein(i.e. the O. volvulus full-length cDNA is only about 37% the size of theD. immitis full-length nucleic acid molecule). The B. malayi ankyrinnucleic acid molecule disclosed herein, encoding a non-full-lengthankyrin protein, spans a region of the B. malayi ankyrin gene that hasno similarity to the O. volvulus E1 nucleic acid molecule and protein,i.e., the B. malayi nucleic acid molecule disclosed herein is in aregion 5' to the region that would correspond to the O. volvulus E1nucleic acid molecule and protein.

One embodiment of the present invention is an isolated protein thatincludes a Dirofilaria ankyrin protein or a Brugia ankyrin protein. Itis to be noted that the term "a" or "an" entity refers to one or more ofthat entity; for example, a protein refers to one or more proteins or atleast one protein. As such, the terms "a" (or "an"), "one or more" and"at least one" can be used interchangeably herein. It is also to benoted that the terms "comprising", "including", and "having" can be usedinterchangeably. According to the present invention, an isolated, orbiologically pure, protein, is a protein that has been removed from itsnatural milieu. As such, "isolated" and "biologically pure" do notnecessarily reflect the extent to which the protein has been purified.An isolated protein of the present invention can be obtained from itsnatural source, can be produced using recombinant DNA technology, or canbe produced by chemical synthesis.

As used herein, an isolated ankyrin protein of the present invention(i.e., a Dirofilaria ankyrin protein or a Brugia ankyrin protein) can bea full-length protein or any homolog of such a protein. An isolatedprotein of the present invention, including a homolog, can be identifiedin a straight-forward manner by the protein's ability to elicit animmune response against a Dirofilaria ankyrin protein or a Brugiaankyrin protein. Examples of Dirofilaria and Brugia ankyrin homologsinclude Dirofilaria and Brugia ankyrin proteins in which amino acidshave been deleted (e.g., a truncated version of the protein, such as apeptide), inserted, inverted, substituted and/or derivatized (e.g., byglycosylation, phosphorylation, acetylation, myristoylation,prenylation, palmitoylation, amidation and/or addition ofglycerophosphatidyl inositol) such that the homolog includes at leastone epitope capable of eliciting an immune response against aDirofilaria or Brugia ankyrin protein, and/or of binding to an antibodydirected against a Dirofilaria or Brugia ankyrin protein. That is, whenthe homolog is administered to an animal as an immunogen, usingtechniques known to those skilled in the art, the animal will produce animmune response against at least one epitope of a natural Dirofilaria orBrugia ankyrin protein. The ability of a protein to effect an immuneresponse can be measured using techniques known to those skilled in theart. As used herein, the term "epitope" refers to the smallest portionof a protein or other antigen capable of selectively binding to theantigen binding site of an antibody or a T-cell receptor. It is wellaccepted by those skilled in the art that the minimal size of a proteinepitope is about six to seven amino acids.

Dirofilaria and Brugia ankyrin protein homologs can be the result ofnatural allelic variation or natural mutation. Dirofilaria and Brugiaankyrin protein homologs of the present invention can also be producedusing techniques known in the art including, but not limited to, directmodifications to the protein or modifications to the gene encoding theprotein using, for example, classic or recombinant DNA techniques toeffect random or targeted mutagenesis.

Ankyrin proteins of the present invention are encoded by Dirofilariaankyrin nucleic acid molecules or Brugia ankyrin nucleic acid molecules.As used herein, a Dirofilaria or Brugia ankyrin nucleic acid moleculeincludes nucleic acid sequences related to a natural Dirofilaria orBrugia ankyrin gene, and preferably, to a D. immitis or a B. malayiankyrin gene. As used herein, a Dirofilaria or Brugia ankyrin geneincludes all regions such as regulatory regions that control productionof the Dirofilaria or Brugia ankyrin protein encoded by the gene (suchas, but not limited to, transcription, translation or post-translationcontrol regions) as well as the coding region itself, and any introns ornon-translated coding regions. As used herein, a gene that "includes" or"comprises" a sequence may include that sequence in one contiguousarray, or may include the sequence as fragmented exons. As used herein,the term "coding region" refers to a continuous linear array ofnucleotides that translates into a protein. A full-length coding regionis that coding region that is translated into a full-length, i.e., acomplete protein as would be initially translated in its naturalmillieu, prior to any post-translational modifications. In oneembodiment, a D. immitis ankyrin gene of the present invention includesthe nucleic acid sequence SEQ ID NO:32, as well as the complement of SEQID NO:32. Nucleic acid sequence SEQ ID NO:32 represents the deducedsequence of the coding strand of a cDNA (complementary DNA) denotedherein as D. immitis ankyrin nucleic acid molecule nDiAnk₅₅₀₃, theproduction of which is disclosed in the Examples. Nucleic acid moleculenDiAnk₅₅₀₃ comprises an apparently full-length coding region. Thecomplement of SEQ ID NO:32 (represented herein by SEQ ID NO:34) refersto the nucleic acid sequence of the strand complementary to the strandhaving SEQ ID NO:32, which can easily be determined by those skilled inthe art. Likewise, a nucleic acid sequence complement of any nucleicacid sequence of the present invention refers to the nucleic acidsequence of the nucleic acid strand that is complementary to (i.e., canform a double helix with) the strand for which the sequence is cited. Itshould be noted that since nucleic acid sequencing technology is notentirely error-free, SEQ ID NO:32 (as well as other nucleic acid andprotein sequences presented herein) represents an apparent nucleic acidsequence of the nucleic acid molecule encoding a D. immitis ankyrinprotein of the present invention.

In another embodiment, a D. immitis ankyrin gene or nucleic acidmolecule can be an allelic variant that includes a similar but notidentical sequence to SEQ ID NO:32, SEQ ID NO:34, or any other D.immitis nucleic acid sequence cited herein. An allelic variant of a D.immitis ankyrin gene including SEQ ID NO:32 and SEQ ID NO:34, is a genethat occurs at essentially the same locus (or loci) in the genome as thegene including SEQ ID NO:32 and SEQ ID NO:34, but which, due to naturalvariations caused by, for example, mutation or recombination, has asimilar but not identical sequence. Because natural selection typicallyselects against alterations that affect function, allelic variantsusually encode proteins having similar activity to that of the proteinencoded by the gene to which they are being compared. Allelic variantsof genes or nucleic acid molecules can also comprise alterations in the5' or 3' untranslated regions of the gene (e.g., in regulatory controlregions), or can involve alternative splicing of a nascent transcript,thereby bringing alternative exons into juxtaposition. Similarly, a B.malayi ankyrin gene or nucleic acid molecule can be an allelic variantthat includes a similar but not identical sequence to SEQ ID NO:37 andSEQ ID NO:39. Allelic variants are well known to those skilled in theart and would be expected to be found within a given parasitic helminthsuch as Dirofilaria or Brugia, since the respective genomes are diploid,and sexual reproduction will result in the reassortment of alleles.

The minimal size of an ankyrin protein homolog of the present inventionis a size sufficient to be encoded by a nucleic acid molecule capable offorming a stable hybrid (i.e., hybridize under stringent hybridizationconditions) with the complementary sequence of a nucleic acid moleculeencoding the corresponding natural protein. As used herein, "stringenthybridization conditions" refer to those experimental conditions underwhich nucleic acid molecules having similar nucleic acid sequences willanneal to each other. Stringent hybridization conditions typicallypermit the hybridization of nucleic acid molecules having at least about70% nucleic acid sequence identity with the nucleic acid molecule beingused as a probe in the hybridization reaction. Formulae to calculate theappropriate hybridization and wash conditions to achieve hybridizationpermitting 30% or less mis-match between two nucleic acid molecules aredisclosed, for example, in Meinkoth et al., 1984, Anal. Biochem 138,267-284. Meinkoth et al., ibid, is by reference herein in its entirety.

Briefly, at page 269, column 1, Meinkoth et al. teach the following:"The formation of nucleic acid hybrids is a reversible process and anunderstanding of the parameters which affect their stability enable oneto derive the optimal conditions for discriminating between perfect andimperfect hybrids. The melting temperature (T_(m)) is affected by ionicstrength (M, in mol/liter), base composition (% G +C), the length of theshortest chain in the duplex (n), and the concentration of helixdestabilizing agents such as formamide. . . . The following equation hasbeen derived from analyzing the influence of these factors on hybridstability:

    T.sub.m =81.5° C.+16.6 log M+0.41(% G+C)-500/n-0.61(% formamide).

This equation pertains to probes longer than approximately 50nucleotides. Hybrids between oligonucleotides (14-20 bp) and immobilizedDNA show decreased stability . . . and an empirical formula has beendetermined to define the optimal conditions for their hybridization. . .. The temperature at which 50% of these short duplexes dissociate(T_(d)) when the hybridization is performed under standard conditions(e.g., 0.9 M NaCl) is:

    T.sub.d (° C.)=4(G +C)+2(A+T)

where G, C, A, and T indicate the number of the correspondingnucleotides in the oligomer. A temperature 5° below the T_(d) is used todetect hybridization between perfectly matched molecules. . . .

The stability of duplexes formed between strands with mismatched basesis decreased according to the number and location of the mismatches andis especially pronounced for short (e.g., 14 bp) oligonucleotides. Forhybrids longer than 150 bp, the T_(m) of a DNA duplex decreases by 1° C.with every 1% of base pairs which are mismatched. . . . For hybridsshorter than 20 bp, the T_(m) decreases by approximately 5° C. for everymismatched base pair. . . . In order to minimize the hybridization ofprobe to related but nonidentical sequences, hybridization reactionsmust be performed under the most stringent conditions possible. From thediscussion above, hybridization stringency can be altered by adjustingthe salt and/or formamide concentrations and/or by changing thetemperature. The stringency can be adjusted either during thehybridization step, or in the posthybridization washes. . . . It isoften convenient to perform the hybridization at low stringencies andwash at increasing stringencies, analyzing the results after each wash.This enables the detection of related sequences and the monitoring ofthe effectiveness of the washes in removing these sequences. Thisstrategy also enables one to obtain an estimate of sequence relatedness.. . . As such, the size of the nucleic acid molecule encoding such aprotein homolog is dependent on nucleic acid composition and percenthomology between the nucleic acid molecule and complementary sequence.It should also be noted that the extent of homology required to form astable hybrid can vary depending on whether the homologous sequences areinterspersed throughout the nucleic acid molecules or are clustered(i.e., localized) in distinct regions on the nucleic acid molecules. Theminimal size of such nucleic acid molecules is typically at least about12 to about 15 nucleotides in length if the nucleic acid molecules areGC-rich and at least about 15 to about 17 bases in length if they areAT-rich. As such, the minimal size of a nucleic acid molecule used toencode an ankyrin protein homolog of the present invention is from about12 to about 18 nucleotides in length. Thus, the minimal size of anankyrin protein homolog of the present invention is from about 4 toabout 6 amino acids in length. There is no limit, other than a practicallimit, on the maximal size of such a nucleic acid molecule in that thenucleic acid molecule can include a portion of a gene, an entire gene,or multiple genes, or portions thereof. The preferred size of a proteinencoded by a nucleic acid molecule of the present invention depends onwhether a full-length, fusion, multivalent, or functional portion ofsuch a protein is desired.

A preferred Dirofilaria or Brugia ankyrin protein of the presentinvention is a compound that when administered to an animal in aneffective manner, is capable of protecting that animal from diseasecaused by a parasitic helminth. In accordance with the presentinvention, the ability of an ankyrin protein of the present invention toprotect an animal from disease by a parasitic helminth refers to theability of that protein to, for example, treat, ameliorate and/orprevent disease caused by parasitic helminths. In one embodiment, aDirofilaria or Brugia ankyrin protein of the present invention canelicit an immune response (including a humoral and/or cellular immuneresponse) against a parasitic helminth.

Suitable parasites to target include any parasite that is essentiallyincapable of causing disease in an animal administered a Dirofilaria orBrugia ankyrin protein of the present invention. As such, parasites totarget includes any parasite that produces a protein having one or moreepitopes that can be targeted by a humoral and/or cellular immuneresponse against a Dirofilaria or Brugia ankyrin protein of the presentinvention and/or that can be targeted by an inhibitory compound thatotherwise inhibits ankyrin function (e.g., a compound that binds toankyrin thereby blocking parasite development and/or migrationregulatory pathways), thereby resulting in the decreased ability of theparasite to cause disease in an animal. Preferred parasitic helminths totarget include nematodes, cestodes, and trematodes, with nematodes beingpreferred. Preferred nematodes to target include filariid, ascarid,capillarid, strongylid, strongyloides, trichostrongyle, and trichuridnematodes. Particularly preferred nematodes are those of the generaAcanthocheilonema, Aelurostrongylus, Ancylostoma, Angiostrongylus,Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma,Dictyocaulus, Dioctophyme, Dipetalonema, Diphyllobothrium, Diplydium,Dirofilaria, Dracunculus, Enterobius, Filaroides, Haemonchus,Lagochilascaris, Loa, Mansonella, Muellerius, Nanophyetus, Necator,Nematodirus, Oesophagostomum, Onchocerca, Opisthorchis, Ostertagia,Parafilaria, Paragonimus, Parascaris, Physaloptera, Protostrongylus,Setaria, Spirocerca, Spirometra, Stephanofilaria, Strongyloides,Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella,Trichostrongylus, Trichuris. Uncinaria, and Wuchereria. Preferredfilariid nematodes include Dirofilaria, Onchocerca, Acanthocheilonema,Brugia, Dipetalonema, Loa, Parafilaria, Setaria, Stephanofilaria andWuchereria filariid nematodes, with D. immitis and B. malayi being evenmore preferred.

The present invention also includes mimetopes of Dirofilaria and Brugiaankyrin proteins of the present invention. As used herein, a mimetope ofa Dirofilaria or Brugia ankyrin protein of the present invention refersto any compound that is able to mimic the activity of such an ankyrinprotein, often because the mimetope has a structure that mimics theparticular ankyrin protein. Mimetopes can be, but are not limited to:peptides that have been modified to decrease their susceptibility todegradation such as all-D retro peptides; anti-idiotypic and/orcatalytic antibodies, or fragments thereof; non-proteinaceousimmunogenic portions of an isolated protein (e.g., carbohydratestructures); and synthetic or natural organic molecules, includingnucleic acids. Such mimetopes can be designed using computer-generatedstructures of proteins of the present invention. Mimetopes can also beobtained by generating random samples of molecules, such asoligonucleotides, peptides or other organic molecules, and screeningsuch samples by affinity chromatography techniques using thecorresponding binding partner.

One embodiment of a Dirofilaria or Brugia ankyrin protein of the presentinvention is a fusion protein that includes a Dirofilaria or Brugiaankyrin protein-containing domain attached to one or more fusionsegments. Suitable fusion segments for use with the present inventioninclude, but are not limited to, segments that can: enhance a protein'sstability; act as an immunopotentiator to enhance an immune responseagainst a Dirofilaria or Brugia ankyrin protein; and/or assist inpurification of a Dirofilaria or Brugia ankyrin protein (e.g., byaffinity chromatography). A suitable fusion segment can be a domain ofany size that has the desired function (e.g., imparts increasedstability, imparts increased immunogenicity to a protein, and/orsimplifies purification of a protein). Fusion segments can be joined toamino and/or carboxyl termini of the Dirofilaria or Brugiaankyrin-containing domain of the protein and can be susceptible tocleavage in order to enable straight-forward recovery of a Dirofilariaor Brugia ankyrin protein. Fusion proteins are preferably produced byculturing a recombinant cell transformed with a fusion nucleic acidmolecule that encodes a protein including the fusion segment attached toeither the carboxyl and/or amino terminal end of a ankyrin-containingdomain. Preferred fusion segments include a metal binding domain (e.g.,a poly-histidine segment); an immunoglobulin binding domain (e.g.,Protein A; Protein G; T cell; B cell; Fc receptor or complement proteinantibody-binding domains); a sugar binding domain (e.g., a maltosebinding domain); and/or a "tag" domain (e.g., at least a portion ofβ-galactosidase, a strep tag peptide, a T7 tag peptide, a Flag™ peptide,or other domains that can be purified using compounds that bind to thedomain, such as monoclonal antibodies). More preferred fusion segmentsinclude metal binding domains, such as a poly-histidine segment; amaltose binding domain; a strep tag peptide, such as that available fromBiometra in Tampa, Fla.; and an S10 peptide. Examples of particularlypreferred fusion proteins of the present invention includePHIS-PDiANK₃₅₂, PHIS-PDiANK₄₂₂, PHIS-PDiANK₂₈₈, PHIS-PDiANK₈₆₄,PHISDiANK₃₅₂, PHISDiANK₄₂₂, and PHISDiANK₂₈₈ production of which isdisclosed herein.

In another embodiment, a Dirofilaria or Brugia ankyrin protein of thepresent invention also includes at least one additional protein segmentthat is capable of protecting an animal from one or more diseases. Sucha multivalent protective protein can be produced by culturing a celltransformed with a nucleic acid molecule comprising two or more nucleicacid domains joined together in such a manner that the resulting nucleicacid molecule is expressed as a multivalent protective compoundcontaining at least two protective compounds capable of protecting ananimal from diseases caused, for example, by at least one infectiousagent.

Examples of multivalent protective compounds include, but are notlimited to, a Dirofilaria or Brugia ankyrin protein of the presentinvention attached to one or more compounds protective against one ormore other infectious agents, particularly an agent that infects humans,cats, dogs, cattle and/or horses, such as, but not limited to: viruses(e.g., adenoviruses, caliciviruses, coronaviruses, distemper viruses,hepatitis viruses, herpesviruses, immunodeficiency viruses, infectiousperitonitis viruses, leukemia viruses, oncogenic viruses, panleukopeniaviruses, papilloma viruses, parainfluenza viruses, parvoviruses, rabiesviruses, and reoviruses, as well as other cancer-causing orcancer-related viruses); bacteria (e.g., Actinomyces, Bacillus,Bacteroides, Bordetella, Bartonella, Borrelia, Brucella, Campylobacter,Capnocytophaga, Clostridium, Corynebacterium, Coxiella, Dermatophilus,Enterococcus, Ehrlichia, Escherichia, Francisella, Fusobacterium,Haemobartonella, Helicobacter, Klebsiella, L-form bacteria, Leptospira,Listeria, Mycobacteria, Mycoplasma, Neorickettsia, Nocardia,Pasteurella, Peptococcus, Peptostreptococcus, Proteus, Pseudomonas,Rickettsia, Rochalimaea, Salmonella, Shigella, Staphylococcus,Streptococcus, and Yersinia; fungi and fungal-related microorganisms(e.g., Absidia, Acremonium, Alternaria, Aspergillus, Basidiobolus,Bipolaris, Blastomyces, Candida, Chlamydia, Coccidioides, Conidiobolus,Cryptococcus, Curvalaria, Epidermophyton, Exophiala, Geotrichum,Histoplasma, Madurella, Malassezia, Microsporum, Moniliella,Mortierella, Mucor, Paecilomyces, Penicillium, Phialemonium,Phialophora, Prototheca, Pseudallescheria, Pseudomicrodochium, Pythium,Rhinosporidium, Rhizopus, Scolecobasidium, Sporothrix, Stemphylium,Trichophyton, Trichosporon, and Xylohypha; and other parasites (e.g.,Babesia, Balantidium, Besnoitia, Cryptosporidium, Eimeria,Encephalitozoon, Entamoeba, Giardia, Hammondia, Hepatozoon, Isospora,Leishmania, Microsporidia, Neospora, Nosema, Pentatrichomonas,Plasmodium, Pneumocystis, Sarcocystis, Schistosoma, Theileria,Toxoplasma, and Trypanosoma, as well as helminth parasites, such asthose disclosed herein). In one embodiment, a Dirofilaria or Brugiaankyrin protein of the present invention is attached to one or moreadditional compounds protective against heartworm disease,elephantiasis, or hydrocele. In another embodiment, one or moreprotective compounds, such as those listed above, can be included in amultivalent vaccine comprising a Dirofilaria or Brugia ankyrin proteinof the present invention and one or more other protective molecules asseparate compounds.

A preferred isolated protein of the present invention is a proteinencoded by at least one of the following nucleic acid molecules:nDiAnk₉₃₇, nDiAnk₉₃₆, nDiAnk₁₀₂₉, nDiAnk₈₁₀, nDiAnk₆₀₀, nDiAnk₁₂₂₈,nDiAnk₁₂₂₇, nDiAnk₅₇₃, nDiAnk₉₁₁, nDiAnk₉₀₉, nDiAnk₁₀₉₆, nDiAnk₁₀₄₄,nDiAnk₅₅₀₃, nDiAnk₅₂₃₅, nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, nDiAnk₈₆₄, nBmAnk₉₀₈,and nBmAnk₉₀₆, or allelic variants of any of these nucleic acidmolecules. Another preferred isolated protein is encoded by a nucleicacid molecule the having nucleic acid sequence SEQ ID NO:1, SEQ ID NO:4,SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:30, SEQ IDNO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:86, SEQ IDNO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ IDNO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ IDNO:106, SEQ ID NO:138, SEQ ID NO:141, and/or SEQ ID NO:144; or anallelic variant of such a nucleic acid molecule.

Translation of SEQ ID NO:1, the coding strand of nDiAnk₉₃₇, yields aprotein of about 312 amino acids, denoted herein as PDiAnk₃₁₂, the aminoacid sequence of which is presented in SEQ ID NO:2, assuming a firstin-frame codon extending from nucleotide 1 to nucleotide 3 of SEQ IDNO:1. The coding region encoding PDiAnk₃₁₂ is presented herein asnDiAnk₉₃₆, which has the nucleotide sequence SEQ ID NO:4 (the codingstrand) and SEQ ID NO:5 (the complementary strand).

Translation of SEQ ID NO:6, the coding strand of nDiAnk₁₀₂₉, yields aprotein of about 270 amino acids, denoted herein as PDiAnk₂₇₀, the aminoacid sequence of which is presented in SEQ ID NO:7, assuming a firstin-frame codon extending from nucleotide 2 to nucleotide 4 of SEQ IDNO:6, and a termination codon extending from nucleotide 812 tonucleotide 814 of SEQ ID NO:6. The coding region encoding PDiAnk₂₇₀, notincluding the termination codon, is presented herein as nDiAnk₈₁₀, whichhas the nucleotide sequence SEQ ID NO:9 (the coding strand) and SEQ IDNO:10 (the complementary strand). The 147 amino acid residues on theC-terminal end of PDiAnk₃₁₂ lined up with 100% identity to the 147 aminoacid residues on the N-terminal end of PDiAnk₂₇₀. PDiAnk₂₇₀ thusrepresents approximately 123 amino acids of new D. immitis ankyrin aminoacid sequence. The presence of a termination codon and a poly-A tail onnDiAnk₁₀₂₉ indicates that nDiAnk₁₀₂₉ represents the authentic 3' end ofthe D. immitis ankyrin messenger RNA that was reverse-transcribed intocDNA.

Translation of SEQ ID NO:11, the coding strand of nDiAnk₆₀₀, yields aprotein of about 200 amino acids, denoted herein as PDiAnk₂₀₀, the aminoacid sequence of which is presented in SEQ ID NO:12, assuming a firstin-frame codon extending from nucleotide 1 to nucleotide 3 of SEQ IDNO:11. The 14 amino acid residues on the C-terminal end of PDiAnk₂₀₀lined up with 100% identity to the 14 amino acid residues on theN-terminal end of PDiAnk₃₁₂. PDiAnk₂₀₀ thus represents approximately 186amino acids of new D. immitis ankyrin amino acid sequence.

Translation of SEQ ID NO:14, the coding strand of nDiAnk₁₂₂₈, yields aprotein of about 409 amino acids, denoted herein as PDiAnk₄₀₉, the aminoacid sequence of which is presented in SEQ ID NO:15, assuming a firstin-frame codon extending from nucleotide 1 to nucleotide 3 of SEQ IDNO:14. The coding region encoding PDiAnk₄₀₉ is presented herein asnDiAnk₁₂₂₇, which has the nucleotide sequence SEQ ID NO:17 (the codingstrand) and SEQ ID NO:18 (the complementary strand). The 32 amino acidresidues on the C-terminal cnd of PDiAnk₄₀₉ lined up with 100% identityto the 32 amino acid residues on the N-terminal end of PDiAnk₂₀₀.PDiAnk₄₀₉ thus represents about 377 amino acids of new D. immitisankyrin amino acid sequence.

Translation of SEQ ID NO:19, the coding strand of nDiAnk₅₇₃, yields aprotein of about 191 amino acids, denoted herein as PDiAnk₁₉₁, the aminoacid sequence of which is presented in SEQ ID NO:20, assuming a firstin-frame codon extending from nucleotide 1 to nucleotide 3 of SEQ IDNO:19. The 32 amino acid residues on the C-terminal end of PDiAnk₁₉₁lined up with 100% identity to the 32 amino acid residues on theN-terminal end of PDiAnk₄₀₉. PDiAnk₁₉₁ thus represents approximately 159amino acids of new D. immitis ankyrin amino acid sequence.

Translation of SEQ ID NO:22, the coding strand of nDiAnk₉₁₁, yields aprotein of about 303 amino acids, denoted herein as PDiAnk₃₀₃, the aminoacid sequence of which is presented in SEQ ID NO:23, assuming a firstin-frame codon extending from nucleotide 1 to nucleotide 3 of SEQ IDNO:22. The coding region encoding PDiAnk₃₀₃ is presented herein asnDiAnk₉₀₉, which has the nucleotide sequence SEQ ID NO:25 (the codingstrand) and SEQ ID NO:26 (the complementary strand). The 54 amino acidresidues on the C-terminal end of PDiAnk₃₀₃ lined up with 100% identityto the 54 amino acid residues on the N-terminal end of the PDiAnk₄₀₉.PDiAnk₃₀₃ thus represents approximately 249 amino acids of new D.immitis ankyrin amino acid sequence.

Translation of SEQ ID NO:27, the coding strand of nDiAnk₁₀₉₆, yields aprotein of about 348 amino acids, denoted herein as PDiAnk₃₄₈, the aminoacid sequence of which is presented in SEQ ID NO:28, assuming a startcodon extending from nucleotide 51 to nucleotide 53 of SEQ ID NO:27. Thenucleic acid molecule representing the coding region encoding PDiAnk₃₄₈,denoted herein as nDiAnk₁₀₄₄, is presented herein as SEQ ID NO:30 (thecoding strand) and SEQ ID NO:31 (the complementary strand). The about 9amino acid residues on the C-terminal end of PDiAnk₃₄₈ lined up withabout 100% identity to the about 9 amino acid residues on the N-terminalend of the PDiAnk₃₀₃. PDiAnk₃₄₈ thus represents approximately 339 aminoacids of new D. immitis ankyrin amino acid sequence.

Translation of SEQ ID NO:32, the coding strand of nDiAnk₅₅₀₃, yields afull-length polypeptide of about 1745 amino acids, denoted PDiAnk₁₇₄₅,assuming a start codon extending from nucleotide 51 through nucleotide53 of SEQ ID NO:32, and a stop codon extending from nucleotide 5286through nucleotide 5285 of SEQ ID NO:32. The resulting amino acidsequence is presented as SEQ ID NO:33. The coding region encodingPDiAnk₁₇₄₅, not including the termination codon, is denoted herein asnDiANK₅₂₃₅, and has the nucleotide sequence SEQ ID NO:35 (the codingstrand) and SEQ ID NO:36 (the complementary strand). SEQ ID NO:35 ispredicted to encode a protein with a molecular mass of about 191.7 kDand with a predicted pI of about 5.76, as calculated by the DNAsisprogram (available from Hitachi Software, San Bruno, Calif.).

A homology search of a non-redundant protein database was performed withSEQ ID NO:33, using the blastp program available through the BLAST™network of the National Center for Biotechnology Information (NCBI)(National Library of Medicine, National Institutes of Health, Baltimore,Md.), available on the World Wide Web. This database includesSwissProt+PIR+SPupdate+GenPept+GPUpdate+PDB databases. The highestscoring match of the homology search at amino acid level was GenBank™accession number gi|1208874, a C. elegans ankyrin-like protein, to whichSEQ ID NO:33 showed about 69% identity, spanning from about amino acid 1through about amino acid 1745 of SEQ ID NO:33. The second highesthighest scoring match of the homology search at amino acid level wasGenBank™ accession number gi|406288, a human brain ankyrin protein(variant I, Ankyrin_(B)), to which SEQ ID NO:33 showed about 51%identity, spanning from about amino acid 1 through about amino acid1745.

SEQ ID NO:33 was also compared with the protein sequence of the O.volvulus E1 protein as disclosed by Erttmann, et al., 1996a, ibid. Aregion of SEQ ID NO:33 spanning from about amino acid 1282 to aboutamino acid 1745 showed about 78% identity to the 462-amino acid O.volvulus E1 protein. At the nucleotide level, the cDNA encoding SEQ IDNO:33 (i.e., SEQ ID NO:32) was compared to the cDNA encoding the O.volvulus E1 protein. A region of SEQ ID NO:32 spanning from aboutnucleotide 3423 to about nucleotide 5474 showed about 88% nucleic acididentity to the cDNA encoding the O. volvulus E1 protein.

Translation of SEQ ID NO:37, the coding strand of nBmAnk₉₀₈, yields anon-full-length polypeptide of about 302 amino acids, denoted PBmAnk₃₀₂,assuming a first in-frame codon extending from nucleotide 1 throughnucleotide 3 of SEQ ID NO:37. The resulting amino acid sequence ispresented as SEQ ID NO:38. The coding region encoding PBmAnk₃₀₂ isdenoted herein as nBmANK₉₀₆, and has the nucleotide sequence SEQ IDNO:40 (the coding strand) and SEQ ID NO:41 (the complementary strand).

A homology search of a non-redundant protein database was performed onSEQ ID NO:38 using the BLAST network. The homology spans from aboutamino acid 1 through amino acid 302 of SEQ ID NO:38. The highest scoringmatch of the homology search at amino acid level was GenBank accessionnumber A57282, a C. elegans ankyrin-like protein, which was about 86%identical to SEQ ID NO:38 through a region extending from about aminoacid 353 through about amino acid 654 of A57282.

The amino acid sequence of SEQ ID NO:38 was also compared to D. immitisankyrin protein PDiAnk₁₇₄₅ (i.e. SEQ ID NO:33 of the present invention).PBmAnk₃₀₂ had 95% identity to the region of SEQ ID NO:33 spanning fromabout amino acid 341 through about amino acid 642.

Preferred ankyrin proteins of the present invention include proteinsthat are at least about 75%, preferably at least about 80%, morepreferably at least about 85%, even more preferably at least about 90%,and even more preferably at least about 95% identical, and even morepreferably at least about 98% identical to PdiAnk₁₇₄₅, PDiANK₃₅₂,PDiANK₄₂₂, or PDiANK₂₈₈ ; or are at least about 90%, and preferably atleast about 95%, identical to PBmAnk₃₀₂. More preferred are ankyrinproteins comprising PDiAnk₃₁₂, PDiAnk₂₇₀, PDiAnk₂₀₀, PDiAnk₄₀₉,PDiAnk₁₉₁, PDiAnk₃₀₃, PDiAnk₃₄₈, PDiAnk₁₇₄₅, PDiANK₃₅₂, PdiANK₄₂₂,PDiANK₂₈₈ or PBmAnk₃₀₂ ; and proteins encoded by allelic variants of anucleic acid molecules encoding these proteins.

A preferred ankyrin protein of the present invention includes a proteinhaving an amino acid sequence that are at least about 75%, preferably atleast about 80%, more preferably at least about 85%, even morepreferably at least about 90%, and even more preferably at least about95%, and even more preferably at least about 98% identical to SEQ IDNO:33, SEQ ID NO:138, SEQ ID NO:141, SEQ ID NO:144; or a protein havingamino acid sequences that is at least about 90%, and preferably at leastabout 95% identical to SEQ ID NO:38. Another preferred ankyrin proteinof the present invention includes a protein having an amino acidsequence that is at least about 75% identical to SEQ ID NO:33, an aminoacid sequence that is at least about 90% identical to SEQ ID NO:38 anamino acid sequence that is at least about 85% identical to SEQ IDNO:139, an amino acid sequence that is at least about 95% identical toSEQ ID NO:142, an amino acid sequence that is at least about 75%identical to SEQ ID NO:145, an amino acid sequence that is at leastabout 75% identical to SEQ ID NO:161, an amino acid sequence that is atleast about 85% identical to SEQ ID NO:162, an amino acid sequence thatis at least about 85% identical to SEQ ID NO:163, an amino acid sequencethat is at least about 90% identical to SEQ ID NO:165, an amino acidsequence that is at least about 75% identical to SEQ ID NO:166, an aminoacid sequence that is at least about 90% identical to SEQ ID NO:167, anamino acid sequence that is at least about 80% identical to SEQ IDNO:168, an amino acid sequence that is at least about 95% identical toSEQ ID NO:169, an amino acid sequence that is at least about 7 5%identical to SEQ ID NO:170, or an amino acid sequence that is at leastabout 95% identical to SEQ ID NO:171. A more preferred are ankyrinprotein comprises amino acid sequence SEQ ID NO:2, SEQ ID NO:7, SEQ IDNO:12, SEQ ID NO:15, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:28, SEQ IDNO:33, SEQ ID NO:38, SEQ ID NO:139, SEQ ID NO:142, SEQ ID NO:145, SEQ IDNO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:166, SEQID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, and/or SEQ IDNO:171; and an ankyrin protein encoded by an allelic variant of anucleic acid molecule encoding an ankyrin protein having any one ofthese amino acid sequences.

Particularly preferred Dirofilaria ankyrin proteins of the presentinvention comprise amino acid sequence SEQ ID NO:33 (including, but notlimited to, the proteins consisting of amino acid sequence SEQ ID NO:33,fusion proteins and multivalent proteins), and proteins encoded byallelic variants of nucleic acid molecules encoding proteins havingamino acid sequence SEQ ID NO:33; and particularly preferred Brugiaankyrin proteins of the present invention comprise amino acid sequenceSEQ ID NO:38 (including, but not limited to, the proteins consisting ofSEQ ID NO:38, fusion proteins and multivalent proteins), and proteinsencoded by allelic variants of nucleic acid molecules encoding proteinshaving amino acid sequence SEQ ID NO:38.

In one embodiment, a preferred D. immitis or B. malayi ankyrin proteinof the present invention comprises an amino acid sequence of at leastabout 500 amino acids, preferably at least about 1000 amino acids, andeven more preferably at least about 1500 amino acids. Within thisembodiment, a preferred D. immitis ankyrin protein of the presentinvention has an amino acid sequence comprising at least a portion ofSEQ ID NO:33. In another embodiment, a preferred D. immitis or B. malayiankyrin protein comprises a full-length protein, i.e., a protein encodedby a full-length coding region. A particularly preferred apparentlyfull-length ankyrin protein is PDiAnk₁₇₄₅.

Additional preferred ankyrin proteins of the present invention includeproteins encoded by nucleic acid molecules comprising at least a portionof nDiAnk₉₃₇, nDiAnk₉₃₆, nDiAnk₁₀₂₉, nDiAnk₈₁₀, nDiAnk₆₀₀, nDiAnk₁₂₂₈,nDiAnk₁₂₂₇, nDiAnk₅₇₃, nDiAnk₉₁₁, nDiAnk₉₀₉, nDiAnk₁₀₉₆, nDiAnk₁₀₄₄,nDiAnk₅₅₀₃, nDiAnk₅₂₃₅, nBmAnk₉₀₈, nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, nDiAnk₈₆₄,and/or nBmAnk₉₀₆, as well as ankyrin proteins encoded by allelicvariants of these nucleic acid molecules.

Also preferred are ankyrin proteins encoded by nucleic acid moleculeshaving nucleic acid sequences comprising at least a portion of SEQ IDNO:1, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:14,SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:27,SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:40,SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94,SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104,SEQ ID NO:106, SEQ ID NO:138, SEQ ID NO:141, and/or SEQ ID NO:144 aswell as allelic variants of these nucleic acid molecules.

In another embodiment, a preferred Dirofilaria or Brugia ankyrin proteinof the present invention is encoded by a nucleic acid moleculecomprising at least about 1500 nucleotides, preferably at least about3000 nucleotides and more preferably at least about 4500 nucleotides.Within this embodiment is an ankyrin protein encoded by at least aportion nDiAnk₅₅₀₃ or by an allelic variant of this nucleic acidmolecule. In yet another embodiment, a preferred Dirofilaria or Brugiaankyrin protein of the present invention is encoded by a nucleic acidmolecule comprising an apparently full-length ankyrin coding region,i.e., a nucleic acid molecule encoding an apparently full-length ankyrinprotein.

Another embodiment of the present invention is an isolated nucleic acidmolecule comprising either a Dirofilaria ankyrin nucleic acid moleculeor a Brugia ankyrin nucleic acid molecule. The identifyingcharacteristics of such nucleic acid molecules is heretofore described.A nucleic acid molecule of the present invention can include an isolatednatural Dirofilaria or Brugia ankyrin gene or a homolog thereof, thelatter of which is described in more detail below. A nucleic acidmolecule of the present invention can include one or more regulatoryregions, full-length or partial coding regions, or combinations thereof.The minimal size of a nucleic acid molecule of the present invention isa size sufficient to allow the formation of a stable hybrid (i.e.,hybridization under stringent hybridization conditions) with thecomplementary sequence of another nucleic acid molecule. As such, theminimal size of an ankyrin nucleic acid molecule of the presentinvention is from about 12 to about 18 nucleotides in length. Preferredankyrin nucleic acid molecules include D. immitis ankyrin nucleic acidmolecules and B. malayi ankyrin nucleic acid molecules.

In accordance with the present invention, an isolated nucleic acidmolecule is a nucleic acid molecule that has been removed from itsnatural milieu (i.e., that has been subjected to human manipulation) andcan include DNA, RNA, or derivatives of either DNA or RNA. As such,"isolated" does not reflect the extent to which the nucleic acidmolecule has been purified. An isolated Dirofilaria or Brugia ankyrinnucleic acid molecule of the present invention can be isolated from itsnatural source or produced using recombinant DNA technology (e.g.,polymerase chain reaction (PCR) amplification or cloning) or chemicalsynthesis. Isolated Dirofilaria or Brugia ankyrin nucleic acid moleculescan include, for example, natural allelic variants and nucleic acidmolecules modified by nucleotide insertions, deletions, substitutions,and/or inversions in a manner such that the modifications do notsubstantially interfere with the nucleic acid molecule's ability toencode an ankyrin protein of the present invention.

A Dirofilaria or Brugia ankyrin nucleic acid molecule homolog can beproduced using a number of methods known to those skilled in the art,see, for example, Sambrook et al., 1989, Molecular Cloning: A LaboratoryManual, Cold Spring Harbor Labs Press; Sambrook et al., ibid., is hereinincorporated by reference in its entirety. For example, nucleic acidmolecules can be modified using a variety of techniques including, butnot limited to, classic mutagenesis and recombinant DNA techniques suchas site-directed mutagenesis, chemical treatment, restriction enzymecleavage, ligation of nucleic acid fragments, PCR amplification,synthesis of oligonucleotide mixtures and ligation of mixture groups to"build" a mixture of nucleic acid molecules, and combinations thereof.Nucleic acid molecule homologs can be selected by hybridization with aDirofilaria or Brugia ankyrin nucleic acid molecule or by screening thefunction of a protein encoded by the nucleic acid molecule (e.g.,ability to elicit an immune response against at least one epitope of aDirofilaria or Brugia ankyrin protein).

An isolated nucleic acid molecule of the present invention can include anucleic acid sequence that encodes at least one Dirofilaria or Brugiaankyrin protein of the present invention, examples of such proteinsbeing disclosed herein. Although the phrase "nucleic acid molecule"primarily refers to the physical nucleic acid molecule and the phrase"nucleic acid sequence" primarily refers to the sequence of nucleotideson the nucleic acid molecule, the two phrases can be usedinterchangeably, especially with respect to a nucleic acid molecule, ora nucleic acid sequence, being capable of encoding a Dirofilaria orBrugia ankyrin protein.

A preferred nucleic acid molecule of the present invention, whenadministered to an animal, is capable of protecting that animal fromdisease caused by a parasitic helminth. As will be disclosed in moredetail below, such a nucleic acid molecule can be, or encode, anantisense RNA, a molecule capable of triple helix formation, a ribozyme,or other nucleic acid-based drug compound. In additional embodiments, anucleic acid molecule of the present invention can encode a protectiveprotein (e.g., an ankyrin protein of the present invention), the nucleicacid molecule being delivered to the animal, for example, by directinjection (i.e, as a genetic vaccine) or in a vehicle such as arecombinant virus vaccine or a recombinant cell vaccine.

One embodiment of the present invention is an ankyrin nucleic acidmolecule comprising all or part of nucleic acid molecules nDiAnk₉₃₇,nDiAnk₉₃₆, nDiAnk₁₀₂₉, nDiAnk₈₁₀, nDiAnk₆₀₀, nDiAnk₁₂₂₈, nDiAnk₁₂₂₇,nDiAnk₅₇₃, nDiAnk₉₁₁, nDiAnk₉₀₉, nDiAnk₁₀₉₆, nDiAnk₁₀₄₄, nDiAnk₅₅₀₃,nDiAnk₅₂₃₅, nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, nDiAnk₈₆₄, nBmAnk₉₀₈, or nBmAnk₉₀₆,or allelic variants of these nucleic acid molecules. Another preferrednucleic acid molecule of the present invention includes at least aportion of nucleic acid sequence SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4,SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ IDNO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ IDNO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ IDNO:31, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:86, SEQ IDNO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ IDNO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ IDNO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ IDNO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQID NO:107, SEQ ID NO:138, SEQ ID NO:141, and/or SEQ ID NO:144, as wellas allelic variants of nucleic acid molecules having these nucleic acidsequences. Such nucleic acid molecules can include nucleotides inaddition to those included in the SEQ ID NOs, such as, but not limitedto, a full-length gene, a full-length coding region, a nucleic acidmolecule encoding a fusion protein, or a nucleic acid molecule encodinga multivalent protective compound.

In one embodiment, an ankyrin nucleic acid molecule of the presentinvention encodes a protein that is at least about 75%, preferably atleast about 80%, more preferably at least about 85%, even morepreferably at least about 90%, and even more preferably at least about95% identical to PDiAnk₁₇₄₅ ; or is at least about 90%, and preferablyat least about 95%, identical to PBmAnk₃₀₂. Even more preferred is anucleic acid molecule encoding PDiAnk₃₁₂, PDiAnk₂₇₀, PDiAnk₂₀₀,PDiAnk₄₀₉, PDiAnk₁₉₁, PDiAnk₃₀₃, PDiAnk₃₄₈, PDiAnk₁₇₄₅, PBmAnk₃₀₂,and/or an allelic variant of such a nucleic acid molecule.

In another embodiment, an ankyrin nucleic acid molecule of the presentinvention encodes a protein having an amino acid sequence that is atleast about 75%, preferably at least about 80%, more preferably at leastabout 85%, even more preferably at least about 90%, and even morepreferably at least about 95% identical to SEQ ID NO:33; or is at leastabout 90%, and preferably at least about 95%, identical to SEQ ID NO:38.The present invention also includes an ankyrin nucleic acid moleculeencoding a protein having at least a portion of SEQ ID NO:2, SEQ IDNO:7, SEQ ID NO:12, SEQ ID NO:15, SEQ ID NO:20, SEQ ID NO:23, SEQ IDNO:28, SEQ ID NO:33 SEQ ID NO:38, SEQ ID NO:139, SEQ ID NO:142, SEQ IDNO:145, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:165, SEQID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170,and/or SEQ ID NO:171, as well as allelic variants of an ankyrin nucleicacid molecule encoding a protein having these sequences, includingnucleic acid molecules that have been modified to accommodate codonusage properties of the cells in which such nucleic acid molecules areto be expressed.

In another embodiment, a preferred Dirofilaria or Brugia ankyrin nucleicacid molecule encodes an ankyrin protein comprising at least about 500amino acids, preferably at least about 1000 amino acids, and morepreferably at least about 1500 amino acids; i.e., an ankyrin nucleicacid molecule that comprises a contiguous ankyrin coding region of atleast about 1500 nucleotides, preferably at least about 3000nucleotides, and more preferably at least about 4500 nucleotides.

In yet another embodiment, a preferred Dirofilaria or Brugia ankyrinnucleic acid molecule of the present invention comprises an apparentlyfull-length ankyrin coding region, i.e., the preferred nucleic acidmolecule encodes an apparently full-length ankyrin protein.

Knowing the nucleic acid sequences of certain Dirofilaria or Brugiaankyrin nucleic acid molecules of the present invention allows oneskilled in the art to, for example, (a) make copies of those nucleicacid molecules, (b) obtain nucleic acid molecules including at least aportion of such nucleic acid molecules (e.g., nucleic acid moleculesincluding full-length genes, full-length coding regions, regulatorycontrol sequences, truncated coding regions), and (c) obtain otherDirofilaria or Brugia ankyrin nucleic acid molecules. Such nucleic acidmolecules can be obtained in a variety of ways including screeningappropriate expression libraries with antibodies of the presentinvention, or amplifying genomic DNA; traditional cloning techniquesusing oligonucleotide probes of the present invention to screenappropriate libraries; and PCR amplification of appropriate libraries orDNA using oligonucleotide primers of the present invention. Preferredlibraries to screen or from which to amplify nucleic acid moleculesinclude Dirofilaria or Brugia L3, L4 or adult cDNA libraries as well asgenomic DNA libraries. Similarly, preferred DNA sources from which toamplify nucleic acid molecules include Dirofilaria or Brugia L3, L4 oradult cDNA and genomic DNA. Techniques to clone and amplify genes aredisclosed, for example, in Sambrook et al., ibid.

The present invention also includes nucleic acid molecules that areoligonucleotides capable of hybridizing, under stringent hybridizationconditions, with complementary regions of other, preferably longer,nucleic acid molecules of the present invention such as those comprisingDirofilaria or Brugia ankyrin nucleic acid molecules or other parasitichelminth ankyrin nucleic acid molecules. Oligonucleotides of the presentinvention can be RNA, DNA, or derivatives of either. The minimum size ofsuch oligonucleotides is the size required for formation of a stablehybrid between an oligonucleotide and a complementary sequence on anucleic acid molecule of the present invention. A preferredoligonucleotide of the present invention has a maximum size of about 100nucleotides. The present invention includes oligonucleotides that can beused as, for example, probes to identify nucleic acid molecules, primersto produce nucleic acid molecules, or therapeutic reagents to inhibitDirofilaria or Brugia ankyrin protein production or activity (e.g., asantisense-, triplex formation-, ribozyme- and/or RNA drug-basedreagents). The present invention also includes the use of sucholigonucleotides to protect animals from disease using one or more ofsuch technologies. Appropriate oligonucleotide-containing therapeuticcompositions can be administered to an animal using techniques known tothose skilled in the art.

One embodiment of the present invention includes a recombinant vector,which includes at least one isolated nucleic acid molecule of thepresent invention, inserted into any vector capable of delivering thenucleic acid molecule into a host cell. Such a vector containsheterologous nucleic acid sequences, that is nucleic acid sequences thatare not naturally found adjacent to nucleic acid molecules of thepresent invention and that preferably are derived from a species otherthan the species from which the nucleic acid molecule(s) are derived.The vector can be either RNA or DNA, either prokaryotic or eukaryotic,and typically is a virus or a plasmid. Recombinant vectors can be usedin the cloning, sequencing, and/or otherwise manipulating of Dirofilariaand Brugia ankyrin nucleic acid molecules of the present invention.

One type of recombinant vector, referred to herein as a recombinantmolecule, comprises a nucleic acid molecule of the present inventionoperatively linked to an expression vector. The phrase operativelylinked refers to insertion of a nucleic acid molecule into an expressionvector in a manner such that the molecule is able to be expressed whentransformed into a host cell. As used herein, an expression vector is aDNA or RNA vector that is capable of transforming a host cell and ofeffecting expression of a specified nucleic acid molecule. Preferably,the expression vector is also capable of replicating within the hostcell. Expression vectors can be either prokaryotic or eukaryotic, andare typically viruses or plasmids. Expression vectors of the presentinvention include any vectors that function (i.e., direct geneexpression) in recombinant cells of the present invention, including inbacterial, fungal, parasite, insect, other animal, and plant cells.Preferred expression vectors of the present invention can direct geneexpression in bacterial, yeast, helminth or other parasite, insect andmammalian cells, and more preferably in the cell types disclosed herein.

In particular, expression vectors of the present invention containregulatory sequences such as transcription control sequences,translation control sequences, origins of replication, and otherregulatory sequences that are compatible with the recombinant cell andthat control the expression of nucleic acid molecules of the presentinvention. In particular, recombinant molecules of the present inventioninclude transcription control sequences. Transcription control sequencesare sequences which control the initiation, elongation, and terminationof transcription. Particularly important transcription control sequencesare those which control transcription initiation, such as promoter,enhancer, operator and repressor sequences. Suitable transcriptioncontrol sequences include any transcription control sequence that canfunction in at least one of the recombinant cells of the presentinvention. A variety of such transcription control sequences are knownto those skilled in the art. Preferred transcription control sequencesinclude those which function in bacterial, yeast, helminth or otherendoparasite, or insect and mammalian cells, such as, but not limitedto, tac, lac, trp, trc, oxy-pro, omp/lpp, rrnB, bacteriophage lambda(such as lambda p_(L) and lambda p_(R) and fusions that include suchpromoters), bacteriophage T7, T7lac, bacteriophage T3, bacteriophageSP6, bacteriophage SP01, metallothionein, alpha-mating factor, Pichiaalcohol oxidase, alphavirus subgenomic promoter, antibiotic resistancegene, baculovirus, Heliothis zea insect virus, vaccinia virus,herpesvirus, raccoon poxvirus, other poxvirus, adenovirus,cytomegalovirus (such as immediate early promoter), simian virus 40,retrovirus, actin, retroviral long terminal repeat, Rous sarcoma virus,heat shock, phosphate and nitrate transcription control sequences aswell as other sequences capable of controlling gene expression inprokaryotic or eukaryotic cells. Additional suitable transcriptioncontrol sequences include tissue-specific promoters and enhancers aswell as lymphokine-inducible promoters (e.g., promoters inducible byinterferons or interleukins). Transcription control sequences of thepresent invention can also include naturally occurring transcriptioncontrol sequences naturally associated with parasitic helminths, such asD immitis or B. malayi transcription control sequences.

Suitable and preferred nucleic acid molecules to include in recombinantvectors of the present invention are as disclosed herein. Preferrednucleic acid molecules to include in recombinant vectors, andparticularly in recombinant molecules, include nDiAnk₉₃₇, nDiAnk₉₃₆,nDiAnk₁₀₂₉, nDiAnk₈₁₀, nDiAnk₆₀₀, nDiAnk₁₂₂₈, nDiAnk₁₂₂₇, nDiAnk₅₇₃,nDiAnk₉₁₁, nDiAnk₉₀₉, nDiAnk₁₀₉₆, nDiAnk₁₀₄₄, nDiAnk₅₅₀₃, nDiAnk₅₂₃₅,nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, nDiAnk₈₆₄, nBmAnk₉₀₈, and nBmAnk₉₀₆.Particularly preferred recombinant molecules of the present inventioninclude pTrc-nDiAnk₁₈₆₆, pTrc-nDiAnk₁₀₅₆, pTrc-nDiAnk₁₂₆₆,pTrc-nDiAnk₈₆₄, pTrc-nDiAnk₁₀₅₆, pTrc-nDiAnk₁₂₆₆, and pTrc-nDiAnk₈₆₄,the production of which are described in the Examples section.

Recombinant molecules of the present invention may also (a) containsecretory signals (i.e., signal segment nucleic acid sequences) toenable an expressed parasitic helminth protein of the present inventionto be secreted from the cell that produces the protein and/or (b)contain fusion sequences which lead to the expression of nucleic acidmolecules of the present invention as fusion proteins. Examples ofsuitable signal segments include any signal segment capable of directingthe secretion of a protein of the present invention. Preferred signalsegments include, but are not limited to, tissue plasminogen activator(t-PA), interferon, interleukin, growth hormone, histocompatibility andviral envelope glycoprotein signal segments. Suitable fusion segmentsencoded by fusion segment nucleic acids are disclosed herein. Inaddition, a nucleic acid molecule of the present invention can be joinedto a fusion segment that directs the encoded protein to the proteosome,such as a ubiquitin fusion segment. Eukaryotic recombinant molecules mayalso include intervening and/or untranslated sequences surroundingand/or within the nucleic acid sequences of nucleic acid molecules ofthe present invention.

Another embodiment of the present invention includes a recombinant cellcomprising a host cell transformed with one or more recombinantmolecules of the present invention. Transformation of a nucleic acidmolecule into a cell can be accomplished by any method by which anucleic acid molecule can be inserted into the cell. Transformationtechniques include, but are not limited to, transfection,electroporation, microinjection, lipofection, adsorption, and protoplastfusion. A recombinant cell may remain unicellular or may grow into atissue, organ or a multicellular organism. Transformed nucleic acidmolecules of the present invention can remain extrachromosomal or canintegrate into one or more sites within a chromosome of the transformed(i.e., recombinant) cell in such a manner that their ability to beexpressed is retained. Preferred nucleic acid molecules with which totransform a cell include Dirofilaria and Brugia ankyrin nucleic acidmolecules disclosed herein. Particularly preferred nucleic acidmolecules with which to transform a cell include nDiAnk₉₃₇, nDiAnk₉₃₆,nDiAnk₁₀₂₉, nDiAnk₈₁₀, nDiAnk₆₀₀, nDiAnk₁₂₂₈, nDiAnk₁₂₂₇, nDiAnk₅₇₃,nDiAnk₉₁₁, nDiAnk₉₀₉, nDiAnk₁₀₉₆, nDiAnk₁₀₄₄, nDiAnk₅₅₀₃, nDiAnk₅₂₃₅,nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, nDiAnk₈₆₄, nBmAnk₉₀₈, and nBmAnk₉₀₆.

Suitable host cells to transform include any cell that can betransformed with a nucleic acid molecule of the present invention. Hostcells can be either untransformed cells or cells that are alreadytransformed with at least one nucleic acid molecule (e.g., nucleic acidmolecules encoding one or more proteins of the present invention and/orother proteins useful in the production of multivalent vaccines). Hostcells of the present invention either can be endogenously (i.e.,naturally) capable of producing Dirofilaria or Brugia ankyrin proteinsof the present invention or can be capable of producing such proteinsafter being transformed with at least one nucleic acid molecule of thepresent invention. Host cells of the present invention can be any cellcapable of producing at least one protein of the present invention, andinclude bacterial, fungal (including yeast), parasite (includinghelminth, protozoa and ectoparasite), other insect, other animal andplant cells. Preferred host cells include bacterial, mycobacterial,yeast, helminth, insect and mammalian cells. More preferred host cellsinclude Salmonella, Escherichia, Bacillus, Listeria, Saccharomyces,Spodoptera, Mycobacteria, Trichoplusia, BHK (baby hamster kidney) cells,MDCK cells (Madin-Darby canine kidney cell line), CRFK cells (Crandellfeline kidney cell line), CV-1 cells (African monkey kidney cell lineused, for example, to culture raccoon poxvirus), COS (e.g., COS-7)cells, and Vero cells. Particularly preferred host cells are Escherichiacoli, including E. coli K-12 derivatives; Salmonella typhi; Salmonellatyphimurium, including attenuated strains such as UK-1 χ3987 and SR-11χ4072; Spodoptera frugiperda; Trichoplusia ni; BHK cells; MDCK cells;CRFK cells; CV-1 cells; COS cells; Vero cells; and non-tumorigenic mousemyoblast G8 cells (e.g., ATCC CRL 1246). Additional appropriatemammalian cell hosts include other kidney cell lines, other fibroblastcell lines (e.g., human, murine or chicken embryo fibroblast celllines), myeloma cell lines, Chinese hamster ovary cells, mouse NIH/3T3cells, LMTK³¹ cells and/or HeLa cells. In one embodiment, the proteinsmay be expressed as heterologous proteins in myeloma cell linesemploying immunoglobulin promoters.

A recombinant cell is preferably produced by transforming a host cellwith one or more recombinant molecules, each comprising one or morenucleic acid molecules of the present invention operatively linked to anexpression vector containing one or more transcription controlsequences, examples of which are disclosed herein. Particularlypreferred recombinant molecules include pTrc-nDiAnk₁₈₆₆,pTrc-nDiAnk₁₀₅₆, pTrc-nDiAnk₁₂₆₆, pTrc-nDiAnk₈₆₄, pTrc-nDiAnk₁₀₅₆,pTrc-nDiAnk₁₂₆₆, and pTrc-nDiAnk₈₆₄.

A recombinant cell of the present invention includes any celltransformed with at least one of any nucleic acid molecule of thepresent invention. Suitable and preferred nucleic acid molecules as wellas suitable and preferred recombinant molecules with which to transfercells are disclosed herein. Particularly preferred recombinant cellsinclude E. coli:pTrc-nDiAnk₁₈₆₆, E. coli:pTrc-nDiAnk₁₀₅₆, E.coli:pTrc-nDiAnk₁₂₆₆, E. coli:pTrc-nDiAnk₈₆₄, E. coli:pTrc-nDiAnk₁₀₅₆,E. coli:pTrc-nDiAnk₁₂₆₆, E. coli:pTrc-nDiAnk₈₆₄. Details regarding theproduction of these recombinant cells are disclosed herein.

Recombinant cells of the present invention can also be co-transformedwith one or more recombinant molecules including Dirofilaria or Brugiaankyrin nucleic acid molecules encoding one or more proteins of thepresent invention and one or more other nucleic acid molecules encodingother protective compounds, as disclosed herein (e.g., to producemultivalent vaccines).

Recombinant DNA technologies can be used to improve expression oftransformed nucleic acid molecules by manipulating, for example, thenumber of copies of the nucleic acid molecules within a host cell, theefficiency with which those nucleic acid molecules are transcribed, theefficiency with which the resultant transcripts are translated, and theefficiency of post-translational modifications. Recombinant techniquesuseful for increasing the expression of nucleic acid molecules of thepresent invention include, but are not limited to, operatively linkingnucleic acid molecules to high-copy number plasmids, integration of thenucleic acid molecules into one or more host cell chromosomes, additionof vector stability sequences to plasmids, substitutions ormodifications of transcription control signals (e.g., promoters,operators, enhancers), substitutions or modifications of translationalcontrol signals (e.g., ribosome binding sites, Shine-Dalgarnosequences), modification of nucleic acid molecules of the presentinvention to correspond to the codon usage of the host cell, deletion ofsequences that destabilize transcripts, and use of control signals thattemporally separate recombinant cell growth from recombinant enzymeproduction during fermentation. The activity of an expressed recombinantprotein of the present invention may be improved by fragmenting,modifying, or derivatizing nucleic acid molecules encoding such aprotein.

Isolated Dirofilaria or Brugia ankyrin proteins of the present inventioncan be produced in a variety of ways, including production and recoveryof natural proteins, production and recovery of recombinant proteins,and chemical synthesis of the proteins. In one embodiment, an isolatedprotein of the present invention is produced by culturing a cell capableof expressing the protein under conditions effective to produce theprotein, and recovering the protein. A preferred cell to culture is arecombinant cell of the present invention. Effective culture conditionsinclude, but are not limited to, effective media, bioreactor,temperature, pH and oxygen conditions that permit protein production. Aneffective, medium refers to any medium in which a cell is cultured toproduce a Dirofilaria or Brugia ankyrin protein of the presentinvention. Such medium typically comprises an aqueous medium havingassimilable carbon, nitrogen and phosphate sources, and appropriatesalts, minerals, metals and other nutrients, such as vitamins. Cells ofthe present invention can be cultured in conventional fermentationbioreactors, shake flasks, test tubes, microtiter dishes, and petriplates. Culturing can be carried out at a temperature, pH and oxygencontent appropriate for a recombinant cell. Such culturing conditionsare within the expertise of one of ordinary skill in the art. Examplesof suitable conditions are included in the Examples section.

Depending on the vector and host system used for production, resultantproteins of the present invention may either remain within therecombinant cell; be secreted into the fermentation medium; be secretedinto a space between two cellular membranes, such as the periplasmicspace in E. coli; or be retained on the outer surface of a cell or viralmembrane.

The phrase "recovering the protein", as well as similar phrases, refersto collecting the whole fermentation medium containing the protein andneed not imply additional steps of separation or purification. Proteinsof the present invention can be purified using a variety of standardprotein purification techniques, such as, but not limited to, affinitychromatography, ion exchange chromatography, filtration,electrophoresis, hydrophobic interaction chromatography, gel filtrationchromatography, reverse phase chromatography, concanavalin Achromatography, chromatofocusing and differential solubilization.Proteins of the present invention are preferably retrieved in"substantially pure" form. As used herein, "substantially pure" refersto a purity that allows for the effective use of the protein as atherapeutic composition or diagnostic. A therapeutic composition foranimals, for example, should exhibit no substantial toxicity andpreferably should be capable of stimulating the production of antibodiesin a treated animal.

The present invention also includes isolated (i.e., removed from theirnatural milieu) antibodies that selectively bind to a Dirofilaria orBrugia ankyrin protein of the present invention or a mimetope thereof(e.g., anti-Dirofilaria ankyrin antibodies or anti-Brugia ankyrinantibodies). As used herein, the term "selectively binds to" an ankyrinprotein refers to the ability of antibodies of the present invention topreferentially bind to specified proteins and mimetopes thereof of thepresent invention. Binding can be measured using a variety of methodsstandard in the art including enzyme immunoassays (e.g., ELISA),immunoblot assays, etc.; see, for example, Sambrook et al., ibid., andHarlow, et al., 1988, Antibodies, a Laboratory Manual, Cold SpringHarbor Labs Press; Harlow et al., ibid., is herein incorporated byreference in its entirety. An anti-ankyrin antibody of the presentinvention preferably selectively binds to a Dirofilaria or Brugiaankyrin protein in such a way as to inhibit the function of thatprotein.

Isolated antibodies of the present invention can include antibodies inserum, or antibodies that have been purified to varying degrees.Antibodies of the present invention can be polyclonal or monoclonal, orcan be functional equivalents such as antibody fragments andgenetically-engineered antibodies, including single chain antibodies orchimeric antibodies that can bind to one or more epitopes.

A preferred method to produce antibodies of the present inventionincludes (a) administering to an animal an effective amount of aprotein, peptide or mimetope thereof of the present invention to producethe antibodies and (b) recovering the antibodies. In another method,antibodies of the present invention are produced recombinantly usingtechniques as heretofore disclosed to produce ankyrin proteins of thepresent invention. Antibodies raised against defined proteins ormimetopes can be advantageous because such antibodies are notsubstantially contaminated with antibodies against other substances thatmight otherwise cause interference in a diagnostic assay or side effectsif used in a therapeutic composition.

Antibodies of the present invention have a variety of potential usesthat are within the scope of the present invention. For example, suchantibodies can be used (a) as therapeutic compounds to passivelyimmunize an animal in order to protect the animal from parasitichelminths susceptible to treatment by such antibodies, (b) as reagentsin assays to detect infection by such helminths and/or (c) as tools toscreen expression libraries and/or to recover desired proteins of thepresent invention from a mixture of proteins and other contaminants.Furthermore, antibodies of the present invention can be used to targetcytotoxic agents to parasitic helminths in order to directly kill suchhelminths. Targeting can be accomplished by conjugating (i.e., stablyjoining) such antibodies to the cytotoxic agents using techniques knownto those skilled in the art. Suitable cytotoxic agents are known tothose skilled in the art.

One embodiment of the present invention is a therapeutic compositionthat, when administered to an animal in an effective manner, is capableof protecting that animal from disease caused by a parasitic helminth.Therapeutic compositions of the present invention include at least oneof the following protective compounds: an isolated Dirofilaria or Brugiaankyrin protein or a mimetope thereof, an isolated Dirofilaria or Brugiaankyrin nucleic acid molecule, an isolated antibody that selectivelybinds to a Dirofilaria or Brugia ankyrin protein, an inhibitor ofankyrin function identified by its ability to bind to a Dirofilaria orBrugia ankyrin protein and thereby impede development and/or migrationof the parasite, and a mixture thereof (i.e., combination of at leasttwo of the compounds). As used herein, a protective compound refers to acompound that, when administered to an animal in an effective manner, isable to treat, ameliorate, and/or prevent disease caused by a parasitichelminth. Preferred helminths to target are heretofore disclosed.Examples of proteins, nucleic acid molecules, antibodies and inhibitorsof the present invention are disclosed herein.

The present invention also includes a therapeutic composition comprisingat least one Dirofilaria or Brugia ankyrin-based compound of the presentinvention in combination with at least one additional compoundprotective against one or more infectious agents. Examples of suchcompounds and infectious agents are disclosed herein.

Therapeutic compositions of the present invention can be administered toany animal susceptible to such therapy, preferably to mammals, and morepreferably to dogs, cats, humans, ferrets, horses, cattle, sheep andother pets, economic food animals and/or zoo animals. Preferred animalsto protect against heartworm disease include dogs, cats, humans andferrets, with dogs and cats being particularly preferred. The preferredanimals to protect against elephantiasis and hydrocele include humans.

In one embodiment, a therapeutic composition of the present inventioncan be administered to the vector in which the parasitic helminthdevelops, such as to a mosquito in order to prevent the spread ofheartworm. Such administration could be oral or by developing transgenicvectors capable of producing at least one therapeutic composition of thepresent invention. In another embodiment, an insect vector, such as amosquito, can ingest therapeutic compositions present in the blood of ahost that has been administered a therapeutic composition of the presentinvention.

In order to protect an animal from disease caused by a parasitichelminth, a therapeutic composition of the present invention isadministered to the animal in an effective manner such that thecomposition is capable of protecting that animal from a disease causedby a parasitic helminth. Therapeutic compositions of the presentinvention can be administered to animals prior to infection in order toprevent infection (i.e., as a preventative vaccine) and/or can beadministered to animals after infection in order to treat disease causedby the parasitic helminth (i.e., as a therapeutic vaccine).

Therapeutic compositions of the present invention can be formulated inan excipient that the animal to be treated can tolerate. Examples ofsuch excipients include water, saline, Ringer's solution, dextrosesolution, Hank's solution, and other aqueous physiologically balancedsalt solutions. Nonaqueous vehicles, such as fixed oils, sesame oil,ethyl oleate, or triglycerides may also be used. Other usefulformulations include suspensions containing viscosity enhancing agents,such as sodium carboxymethylcellulose, sorbitol, or dextran. Excipientscan also contain minor amounts of additives, such as substances thatenhance isotonicity and chemical stability. Examples of buffers includephosphate buffer, bicarbonate buffer and Tris buffer, while examples ofpreservatives include thimerosal, m- or o-cresol, formalin and benzylalcohol. Standard formulations can either be liquid injectables orsolids which can be taken up in a suitable liquid as a suspension orsolution for injection. Thus, in a non-liquid formulation, the excipientcan comprise dextrose, human serum albumin, preservatives, etc., towhich sterile water or saline can be added prior to administration.

In one embodiment of the present invention, a therapeutic compositioncan include an adjuvant. Adjuvants are agents that are capable ofenhancing the immune response of an animal to a specific antigen.Suitable adjuvants include, but are not limited to, cytokines,chemokines, and compounds that induce the production of cytokines andchemokines (e.g., granulocyte macrophage colony stimulating factor(GM-CSF), granulocyte colony stimulating factor (G-CSF), macrophagecolony stimulating factor (M-CSF), colony stimulating factor (CSF),erythropoietin (EPO), interleukin 2 (IL-2), interleukin-3 (IL-3),interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6),interleukin 7 (IL-7), interleukin 8 (IL-8), interleukin 10 (IL-10),interleukin 12 (IL-12), interferon gamma, interferon gamma inducingfactor I (IGIF), transforming growth factor beta, RANTES (regulated uponactivation, normal T-cell expressed and presumably secreted), macrophageinflammatory proteins (e.g., MIP-1 alpha and MIP-1 beta), and Leishmaniaelongation initiating factor (LEIF)); bacterial components (e.g.,endotoxins, in particular superantigens, exotoxins and cell wallcomponents); aluminum-based salts; calcium-based salts; silica;polynucleotides; toxoids; serum proteins, viral coat proteins; blockcopolymer adjuvants (e.g., Hunter's Titermax™ adjuvant (Vaxcel™, Inc.Norcross, Ga.), Ribi adjuvants (Ribi ImmunoChem Research, Inc.,Hamilton, Mont.); and saponins and their derivatives (e.g., Quil A(Superfos Biosector A/S, Denmark). Protein adjuvants of the presentinvention can be delivered in the form of the protein themselves or ofnucleic acid molecules encoding such proteins using the methodsdescribed herein.

In one embodiment of the present invention, a therapeutic compositioncan include a carrier. Carriers include compounds that increase thehalf-life of a therapeutic composition in the treated animal. Suitablecarriers include, but are not limited to, polymeric controlled releasevehicles, biodegradable implants, liposomes, bacteria, viruses, othercells, oils, esters, and glycols.

One embodiment of the present invention is a controlled releaseformulation that is capable of slowly releasing a composition of thepresent invention into an animal. As used herein, a controlled releaseformulation comprises a composition of the present invention in acontrolled release vehicle. Suitable controlled release vehiclesinclude, but are not limited to, biocompatible polymers, other polymericmatrices, capsules, microcapsules, microparticles, bolus preparations,osmotic pumps, diffusion devices, liposomes, lipospheres, andtransdermal delivery systems. Other controlled release formulations ofthe present invention include liquids that, upon administration to ananimal, form a solid or a gel in situ. Preferred controlled releaseformulations are biodegradable (i.e., bioerodible).

A preferred controlled release formulation of the present invention iscapable of releasing a composition of the present invention into theblood of the treated animal at a constant rate sufficient to attaintherapeutic dose levels of the composition to protect an animal fromdisease caused by parasitic helminths. The therapeutic composition ispreferably released over a period of time ranging from about 1 to about12 months. A controlled release formulation of the present invention iscapable of effecting a treatment preferably for at least about 1 month,more preferably for at least about 3 months, even more preferably for atleast about 6 months, even more preferably for at least about 9 months,and even more preferably for at least about 12 months.

Therapeutic compositions of the present invention can be administered toanimals prior to infection in order to prevent infection and/or can beadministered to animals after infection in order to treat disease causedby the parasitic helminth. For example, proteins, mimetopes thereof, andantibodies thereof can be used as immunotherapeutic agents. Acceptableprotocols to administer therapeutic compositions in an effective mannerinclude individual dose size, number of doses, frequency of doseadministration, and mode of administration. Determination of suchprotocols can be accomplished by those skilled in the art. A suitablesingle dose is a dose that is capable of protecting an animal fromdisease when administered one or more times over a suitable time period.For example, a preferred single dose of a protein, mimetope or antibodytherapeutic composition is from about 1 microgram (μg) to about 10milligrams (mg) of the therapeutic composition per kilogram body weightof the animal. Booster vaccinations can be administered from about 2weeks to several years after the original administration. Boosteradministrations preferably are administered when the immune response ofthe animal becomes insufficient to protect the animal from disease. Apreferred administration schedule is one in which from about 10 μg toabout 1 mg of the therapeutic composition per kg body weight of theanimal is administered from about one to about two times over a timeperiod of from about 2 weeks to about 12 months. Modes of administrationcan include, but are not limited to, subcutaneous, intradermal,intravenous, intranasal, oral, transdermal and intramuscular routes.

According to one embodiment, a nucleic acid molecule of the presentinvention can be administered to an animal in a fashion to enableexpression of that nucleic acid molecule into a protective protein orprotective RNA (e.g., antisense RNA, ribozyme, triple helix forms or RNAdrug) in the animal. Nucleic acid molecules can be delivered to ananimal in a variety of methods including, but not limited to, (a)administering a naked (i.e., not packaged in a viral coat or cellularmembrane) nucleic acid as a genetic vaccine (e.g., as naked DNA or RNAmolecules, such as is taught, for example in Wolff et al., 1990, Science247, 1465-1468) or (b) administering a nucleic acid molecule packaged asa recombinant virus vaccine or as a recombinant cell vaccine (i.e., thenucleic acid molecule is delivered by a viral or cellular vehicle).

A genetic (i.e., naked nucleic acid) vaccine of the present inventionincludes a nucleic acid molecule of the present invention and preferablyincludes a recombinant molecule of the present invention that preferablyis replication, or otherwise amplification, competent. A genetic vaccineof the present invention can comprise one or more nucleic acid moleculesof the present invention in the form of, for example, a dicistronicrecombinant molecule. Preferred genetic vaccines include at least aportion of a viral genome (i.e., a viral vector). Preferred viralvectors include those based on alphaviruses, poxviruses, adenoviruses,herpesviruses, picornaviruses, and retroviruses, with those based onalphaviruses (such as sindbis or Semliki forest virus), species-specificherpesviruses and poxviruses being particularly preferred. Any suitabletranscription control sequence can be used, including those disclosed assuitable for protein production. Particularly preferred transcriptioncontrol sequences include cytomegalovirus immediate early (preferably inconjunction with Intron-A), Rous sarcoma virus long terminal repeat, andtissue-specific transcription control sequences, as well astranscription control sequences endogenous to viral vectors if viralvectors are used. The incorporation of a "strong" polyadenylation signalis also preferred.

Genetic vaccines of the present invention can be administered in avariety of ways, with intramuscular, subcutaneous, intradermal,transdermal, intranasal and oral routes of administration beingpreferred. A preferred single dose of a genetic vaccine ranges fromabout 1 nanogram (ng) to about 600 μg, depending on the route ofadministration and/or method of delivery, as can be determined by thoseskilled in the art. Suitable delivery methods include, for example, byinjection, as drops, aerosolized and/or topically. Genetic vaccines ofthe present invention can be contained in an aqueous excipient (e.g.,phosphate buffered saline) alone or in a carrier (e.g., lipid-basedvehicles).

A recombinant virus vaccine of the present invention includes arecombinant molecule of the present invention that is packaged in aviral coat and that can be expressed in an animal after administration.Preferably, the recombinant molecule is packaging- orreplication-deficient and/or encodes an attenuated virus. A number ofrecombinant viruses can be used, including, but not limited to, thosebased on alphaviruses, poxviruses, adenoviruses, herpesviruses,picomaviruses, and retroviruses. Preferred recombinant virus vaccinesare those based on alphaviruses (such as Sindbis virus), raccoonpoxviruses, species-specific herpesviruses and species-specificpoxviruses. An example of methods to produce and use alphavirusrecombinant virus vaccines are disclosed in PCT Publication No. WO94/17813, by Xiong et al., published Aug. 18, 1994, which is hereinincorporated by reference in its entirety.

When administered to an animal, a recombinant virus vaccine of thepresent invention infects cells within the immunized animal and directsthe production of a protective protein or RNA nucleic acid molecule thatis capable of protecting the animal from disease caused by a parasitichelminth as disclosed herein. For example, a recombinant virus vaccinecomprising an ankyrin nucleic acid molecule of the present invention isadministered according to a protocol that results in the animalproducing a sufficient immune response to protect itself from heartworm.A preferred single dose of a recombinant virus vaccine of the presentinvention is from about 1×10⁴ to about 1×10⁸ virus plaque forming units(pfu) per kilogram body weight of the animal. Administration protocolsare similar to those described herein for protein-based vaccines, withsubcutaneous, intramuscular, intranasal and oral administration routesbeing preferred.

A recombinant cell vaccine of the present invention includes recombinantcells of the present invention that express at least one protein of thepresent invention. Preferred recombinant cells for this embodimentinclude Salmonella, E. coli, Listeria, Mycobacterium, S. frugiperda,yeast, (including Saccharomyces cerevisiae and Pichia pastoris), BHK,CV-1, myoblast G8, COS (e.g., COS-7), Vero, MDCK and CRFK recombinantcells. Recombinant cell vaccines of the present invention can beadministered in a variety of ways but have the advantage that they canbe administered orally, preferably at doses ranging from about 10⁸ toabout 10¹² cells per kilogram body weight. Administration protocols aresimilar to those described herein for protein-based vaccines.Recombinant cell vaccines can comprise whole cells, cells stripped ofcell walls or cell lysates.

The efficacy of a therapeutic composition of the present invention toprotect an animal from disease caused by a parasitic helminth can betested in a variety of ways including, but not limited to, detection ofprotective antibodies (using, for example, proteins or mimetopes of thepresent invention), detection of cellular immunity within the treatedanimal, or challenge of the treated animal with the parasitic helminthto determine whether the treated animal is resistant to disease.Challenge studies can include implantation of chambers includingparasitic helminth larvae into the treated animal and/or directadministration of larvae to the treated animal. In one embodiment,therapeutic compositions can be tested in animal models such as mice.Such techniques are known to those skilled in the art.

One preferred embodiment of the present invention is the use ofDirofilaria or Brugia ankyrin proteins, nucleic acid molecules,antibodies and inhibitors of the present invention, to protect an animalfrom heartworm. It is particularly preferred to prevent L3 that aredelivered to the animal by the mosquito intermediate host from migratingfrom the site of inoculation and/or maturing into adult worms. As such,preferred therapeutic compositions are those that are able to inhibit atleast one step in the portion of the parasite's development cycle thatincludes L3, third molt, L4, fourth molt, immature adult prior toentering the circulatory system. In dogs, this portion of thedevelopment cycle is about 70 days. Particularly preferred therapeuticcompositions include D. immitis ankyrin-based therapeutic compositionsof the present invention. Such compositions include D. immitis ankyrinnucleic acid molecules, D. immitis ankyrin proteins and mimetopesthereof, anti-D. immitis ankyrin antibodies, and inhibitors of D.immitis ankyrin function. Therapeutic compositions are administered toanimals in a manner effective to protect the animals from heartworm.Additional protection may be obtained by administering additionalprotective compounds, including other parasitic helminth proteins,nucleic acid molecules, antibodies and inhibitory compounds, asdisclosed herein.

One therapeutic composition of the present invention includes aninhibitor of Dirofilaria or Brugia ankyrin function, i.e., a compoundcapable of substantially interfering with the function of a Dirofilariaor Brugia ankyrin protein susceptible to inhibition. For example, anisolated protein or mimetope thereof is administered in an amount andmanner that elicits (i.e., stimulates) an immune response that issufficient, upon interaction with a native ankyrin protein, to protectthe animal from the disease. Similarly, an antibody of the presentinvention, when administered to an animal in an effective manner, isadministered in an amount so as to be present in the animal at a titerthat is sufficient, upon interaction of that antibody with a nativeankyrin protein, to protect the animal from the disease, at leasttemporarily. Oligonucleotide nucleic acid molecules of the presentinvention can also be administered in an effective manner, therebyreducing expression of Dirofilaria or Brugia ankyrin proteins in orderto interfere with development of parasitic helminths targeted inaccordance with the present invention. Methods to identify certainfunctions, i.e., protein-binding capabilities, of Dirofilaria or Brugiaankyrin proteins of the present invention are disclosed herein.

One embodiment of the present invention is a method to identify proteinsthat specifically interact with an ankyrin protein of the presentinvention. The method can comprise the steps of a) identifying andisolating a protein-binding domain of an isolated Dirofilaria or Brugiaankyrin protein; b) contacting that protein-binding domain with isolatedparasitic helminth proteins under conditions such that a parasitichelminth protein and the protein-binding domain can selectively interactand/or bind to each other, using, for example, the yeast two-hybridsystem see, for example, Luban, et al., 1995, Curr. Opin. Biotechnol.,6, 59-64; and c) identifying those proteins that specifically bind tothe isolated ankyrin protein-binding domain. Additional methods toidentify protein-protein interactions with the protein-binding domainsof an isolated ankyrin protein of the present invention are known tothose skilled in the art. Examples include Biacore® screening, confocalimmunofluorescent microscopy, and immunoprecipitations.

An inhibitor of ankyrin function can be identified using Dirofilaria orBrugia ankyrin proteins of the present invention. One embodiment of thepresent invention is a method to identify a compound capable ofinhibiting ankyrin function of a parasitic helminth. Such a methodincludes the steps of: (a) identifying a protein binding or regulatoryactivity of an isolated ankyrin protein in vitro; (b) identifying aputative compound capable of binding to and/or inhibiting the identifiedprotein binding or regulatory activity of the isolated ankyrin protein;(c) contacting D. immitis L3 larvae with the putative inhibitorycompound under conditions in which, in the absence of the compound, thelarvae are able to molt to the L4 stage; and (d) determining if theputative compound inhibits molting. Putative inhibitory compounds toscreen include small organic molecules, antibodies (including mimetopesthereof), and ligand analogs. Such compounds are also screened toidentify those that are substantially not toxic in host animals.

Inhibitors of ankyrin function identified by such a method can be testedfor their ability to block development and/or migration of parasitichelminths, and particularly of D. immitis and B. malayi, in vivo.Preferred ankyrin proteins to inhibit are those produced by parasitichelminths, even more preferred ankyrin proteins to inhibit are thoseproduced by filariid nematodes. A particularly preferred inhibitor ofthe present invention is capable of protecting an animal from heartwormdisease, elephantiasis and/or hydrocele. It is also within the scope ofthe present invention to use inhibitors of the present invention totarget diseases caused by parasitic helminths in animals. Compositionscomprising inhibitors of ankyrin function can be administered to animalsin an effective manner to protect animals from disease caused byparasitic helminths, and preferably to protect animals from heartwormdisease, elephantiasis and/or hydrocele. Effective amounts and dosingregimens can be determined using techniques known to those skilled inthe art.

It is also within the scope of the present invention to use isolatedproteins, mimetopes, nucleic acid molecules and antibodies of thepresent invention as diagnostic reagents to detect infection byparasitic helminths. Such diagnostic reagents can be supplemented withadditional compounds that can specifically detect all phases of theparasite's life cycle. Methods to use such diagnostic reagents todiagnose parasitic helminth infection are well known to those skilled inthe art. Suitable and preferred parasitic helminths to detect are thoseto which therapeutic compositions of the present invention are targeted.Particularly preferred parasitic helminths to detect using diagnosticreagents of the present invention are D. immitis and B. malayi.

The following examples are provided for the purposes of illustration andare not intended to limit the scope of the present invention.

EXAMPLES

It is to be noted that the examples include a number of molecularbiology, microbiology, immunology and biochemistry techniques consideredto be familiar to those skilled in the art. Disclosure of suchtechniques can be found, for example, in Sambrook et al., ibid. andAusubel, et al., 1993, Current Protocols in Molecular Biology,Greene/Wiley Interscience, New York, N.Y., and related references.Ausubel, et al., ibid. is herein incorporated by reference in itsentirety. DNA sequence analyses and protein translations were carriedout using the DNAsis program (available from Hitachi Software, SanBruno, Calif.), and the default settings for the analysis program. Itshould also be noted that because nucleic acid sequencing technology,and in particular the sequencing of PCR products, is not entirelyerror-free, that the nucleic acid and deduced protein sequencespresented herein represent apparent nucleic acid sequences of thenucleic acid molecules encoding D. immitis ankyrin proteins of thepresent invention.

Example 1

This example describes the isolation and sequencing of several D.immitis ankyrin nucleic acid molecules. It is to be noted that some ofthe nucleic acid molecules disclosed in this example were isolated byPCR with degenerate primers and/or primers not fully identical to the D.immitis sequences. The authentic D. immitis nucleotide sequences wereverified on overlapping nucleic acid molecules, and thus the nucleotidesequences of the nucleic acid molecules disclosed in this example arefully representative of D. immitis sequences.

A. As a first step in the isolation of a full-length ankyrin cDNAmolecule from D. immitis, a D. immitis ankyrin nucleic acid molecule ofabout 937 nucleotides, denoted herein as nDiAnk₉₃₇, was isolated from aD. immitis cDNA library by PCR amplification for use as a probe, asfollows. A D. immitis 48-hour L3 cDNA library was constructed in theUni-ZAP® XR vector (available from Stratagene Cloning Systems, La Jolla,Calif.), using Stratagene's ZAP-cDNA® Synthesis Kit protocol and L3mRNAs (i.e., messenger RNAs isolated from D. immitis third-stage larvae,harvested at 48 hours). Initially, degenerate primers were designedbased on conserved regions of the C. elegans unc-44 gene described inOtsuka, et al., ibid. These initial attempts to PCR-amplify anankyrin-related nucleic acid molecule from the D. immitis cDNA librarywere unsuccessful. In a second attempt, PCR primers were designed basedon the Onchocerca volvulus E1 gene disclosed in Erttmann, et al., 1996a,ibid. These primers included forward primer OVANKY 554+, having thenucleotide sequence 5' CATCAATTTTTGGAATTTTCTGG 3', denoted herein as SEQID NO:42 and reverse primer OVANKY 1464-, having the nucleotide sequence5' CGTTTACAGCAACATCATCCTC 3', denoted herein as SEQ ID NO:43. Severalattempts to amplify an ankyrin-related nucleic acid molecule from the D.immitis cDNA library with these primers using standard PCR amplificationconditions were likewise unsuccessful. Finally, the same primers wereused in a modified amplification procedure called "touchdown" PCR. Thisprocedure included the following amplification cycles: six cycles of 94°C. for 30 sec, 58° C. for 45 sec, and 72° C. for 3 min; six cycles of94° C. for 30 sec, 56° C. for 45 sec, and 72° C. for 3 min; and 20cycles of 94° C. for 30 sec, 50° C. for 45 sec, and 72° C. for 3 min. Anabout 937-base-pair (bp) DNA fragment was detected in the PCR reactionby agarose gel electrophoresis. The PCR-amplified fragment, denotedherein as nDiAnk₉₃₇, was excised from the gel and purified using theQIAquick™ kit (available from Qiagen, Chatsworth, Calif.) as permanufacturer's instructions. The resultant 937-bp DNA fragment wassubcloned into the pCRII™ vector (available from Invitrogen, San Diego,Calif.) according to the manufacturer's instructions.

The nucleic acid molecule nDiAnk₉₃₇ was sequenced by the Sanger dideoxychain termination method, using the PRISM™ Ready Dye Terminator CycleSequencing Kit with AmpliTaq® DNA Polymerase, FS (available from thePerkin-Elmer Corporation, Norwalk, Conn.). PCR extensions were done inthe GeneAmp™ PCR System 9600 (available from Perkin-Elmer). Excess dyeterminators were removed from extension products using the Centriflex™Gel Filtration Cartridge (available from Advanced Genetics TechnologiesCorporation, Gaithersburg, Md.) following the standard protocol. Sampleswere resuspended according to ABI protocols and were run on aPerkin-Elmer ABI PRISM™ 377 Automated DNA Sequencer. The resultingnucleic acid sequence of nDiAnk₉₃₇ is presented herein as SEQ ID NO:1(the coding strand) and SEQ ID NO:3 (the complementary strand).

Translation of SEQ ID NO:1 yields a protein of about 312 amino acids,denoted herein as PDiAnk₃₁₂, the amino acid sequence of which ispresented in SEQ ID NO:2, assuming a first in-frame codon extending fromnucleotide 1 to nucleotide 3 of SEQ ID NO:1. The coding region encodingPDiAnk₃₁₅ is presented herein as nDiAnk₉₃₆, which has the nucleotidesequence SEQ ID NO:4 (the coding strand) and SEQ ID NO:5 (thecomplementary strand).

B. An additional ankyrin nucleic acid molecule of about 1029 bp,containing the authentic 3' end of a D. immitis ankyrin coding region,was isolated as follows.

Nucleic acid molecule nDiAnk₉₃₇, isolated as disclosed in Example 1A,was used as a hybridization probe to screen a D. immitis 48-hour L3 cDNAlibrary. Nucleic acid molecule nDiAnk₉₃₇ was labeled with α-[³² P]dATPusing the Megaprime™ Kit, available from Amersham, Arlington Heights,Ill. The labeled probe was then hybridized and washed under stringentconditions (i.e., allowing at most about 3% bp mismatch) to about 5×10⁵plaque forming units of an D. immitis 48-hour L3 cDNA library,constructed as disclosed in Example 1A. Fifteen plaques that hybridizedwith the labeled probe were selected and subjected to three rounds ofplaque purification. The size and identity of the bacteriophage clonesthat hybridized with the probe were identified by PCR amplificationusing vector-specific primers, and subsequent Southern hybridization ofthe separated PCR-amplified DNA fragments, using nDiAnk₉₃₇ as a probe.Of these 15 clones, none had inserts larger than about 1.1 kilobases(kb). One positively hybridizing clone having an insert of about 1029 bpwas chosen for further study. The insert from this cDNA clone, denotedherein as nDiAnk₁₀₂₉, was PCR-amplified with a T3/T7 primer set(available from Stratagene), and was subcloned into the pCRIl™ vector.The resulting plasmid, containing nucleic acid molecule nDiAnk₁₀₂₉, wassubjected to automated sequencing as described in Example 1A. Thenucleotide sequence of nDiAnk₁₀₂₉ is presented herein as SEQ ID NO:6(the coding strand) and SEQ ID NO:8 (the complementary strand). The 443nucleotides on the 3' end of nDiAnk₉₃₇ lined up with 100% identity tothe 443 nucleotides on the 5' end of nDiANK₁₀₂₉.

Translation of SEQ ID NO:6 yields a protein of about 270 amino acids,denoted herein as PDiAnk₂₇₀, the amino acid sequence of which ispresented in SEQ ID NO:7, assuming a first in-frame codon extending fromnucleotide 2 to nucleotide 4 of SEQ ID NO:6, and a termination codonextending from nucleotide 812 to nucleotide 814 of SEQ ID NO:6. Thecoding region encoding PDiAnk₂₇₀, not including the termination codon,is presented herein as nDiAnk₈₁₀, which has the nucleotide sequence SEQID NO:9 (the coding strand) and SEQ ID NO:10 (the complementary strand).The 147 amino acid residues on the C-terminal end of PDiAnk₃₁₂(disclosed in Example 1A) lined up with 100% identity to the 147 aminoacid residues on the N-terminal end of PDiAnk₂₇₀. PDiAnk₂₇₀ thusrepresents approximately 123 amino acids of new D. immitis ankyrin aminoacid sequence. The presence of a termination codon and a poly-A tail onnDiAnk₁₀₂₉ indicates that nDiAnk₁₀₂₉ represents the authentic 3' end ofthe D. immitis ankyrin messenger RNA that was reverse-transcribed intocDNA.

C. An additional ankyrin nucleic acid molecule of about 600 bp wasisolated by PCR-amplification from a D. immitis 48-hour L3 cDNA library,as follows.

Since nDiAnk₉₃₇ (isolated as disclosed in Example 1A) extended beyondthe 5' end of nDiAnk₁₀₂₉ (isolated as disclosed in Example 1B) by 495bp, nDiAnk₁₀₂₉ did not appear to represent a full-length ankyrin cDNAmolecule. Furthermore, nDiAnk₉₃₇ did not appear to contain the authentic5' end of a full-length ankyrin cDNA molecule. This result suggestedthat the D. immitis ankyrin messenger RNA was larger, but was notrepresented as cDNA at hybridization-detectable levels in the D. immitisL3 cDNA library utilized in these experiments. Therefore, isolation ofadditional portions of a full-length D. immitis ankyrin nucleic acidmolecule were carried out by PCR amplification. An about 600-bp D.immitis ankyrin nucleic acid molecule was amplified by PCR from a D.immitis 48-hour L3 cDNA library, constructed as described in Example 1A,using primers designed according to ankyrin nucleic acid sequences of D.immitis, derived as described in Example 1A, and O. volvulus, derivedfrom the nucleotide sequence reported in Erttmann, et al., 1996a, ibid.The primers included forward primer OVANKY-1+, having the nucleotidesequence 5' GCACAACCAGTTCCGCAAGAAA 3', denoted herein as SEQ ID NO:44and reverse primer DIANKY-1-, having the nucleotide sequence 5'GGTTATTGGAAGAAGATTTCC 3', denoted herein as SEQ ID NO:45. DIANKY-1- wasdesigned to hybridize to nucleotides 22-42 of SEQ ID NO:1, i.e., about22-42 nucleotides downstream of the 5'-end of nDiAnk₉₃₇. Amplificationwas accomplished using the "touchdown" PCR protocol as described inExample 1A. A PCR product of about 600 bp was observed upon agarose gelelectrophoresis of the PCR reaction, which is denoted herein asnDiAnk₆₀₀. The PCR product was gel purified and subcloned into the pCRIIvector as described in Example 1A. The nucleotide sequence of nDiAnk₆₀₀was determined, and is presented herein as SEQ ID NO:11 (the codingstrand) and SEQ ID NO:13 (the complementary strand). The 42 nucleotideson the 3' end of nDiAnk₆₀₀ lined up with 100% identity to the 42nucleotides on the 5' end of nDiANK₉₃₇ (disclosed in Example 1A).

Translation of SEQ ID NO:11 yields a protein of about 200 amino acids,denoted herein as PDiAnk₂₀₀, the amino acid sequence of which ispresented in SEQ ID NO:12, assuming a first in-frame codon extendingfrom nucleotide 1 to nucleotide 3 of SEQ ID NO:11. The 14 amino acidresidues on the C-terminal end of PDiAnk₂₀₀ lined up with 100% identityto the 14 amino acid residues on the N-terminal end of PDiAnk₃₁₂(disclosed in Example 1A). PDiAnk₂₀₀ thus represents approximately 186amino acids of new D. immitis ankyrin amino acid sequence.

D. An additional D. immitis ankyrin nucleic acid molecule of about 1228bp was isolated from a D. immitis 48-h L3 cDNA library by nested PCR, asfollows.

In order to clone additional D. immitis ankyrin nucleic acid molecules,three degenerate forward primers were designed based on C. elegansUNC-44 DNA sequences reported in Otsuka, et al., ibid. These primerswere paired with various D. immitis reverse primers reverse primers inseveral unsuccessful attempts to isolate additional D. immitis ankyrinnucleic acid molecules from a D. immitis 48-h L3 cDNA library bystandard PCR amplification. Finally, an additional D. immitis ankyrinnucleic acid molecule was isolated when two of the C. elegans-derivedprimers were used with two D. immitis-derived primers in a nested PCR.The two forward primers were: CEANKY-3+, having the nucleotide sequence5' CAYCARGCNGCNCARCARGGNCA 3', denoted herein as SEQ ID NO:46, andCEANKY-4+, having the nucleotide sequence 5' GTNGAYGAYGTNACNGTNGAYTA 3',denoted herein as SEQ ID NO:47. A standard PCR amplification wasperformed using as a template a D. immitis 48-hour L3 cDNA libraryconstructed as described in Example 1A, using forward primer CEANKY-4+and reverse primer DIANKY-1-, as disclosed in Example 1C. No distinctnucleic acid molecules were observed from this PCR reaction upon gelelectrophoresis, but a smear of indistinguishable PCR products wasevident. A very small aliquot of this initial PCR reaction wassubsequently used as a template for a second PCR, using forward primerCEANKY-3+, which was predicted to anneal internal to CEANKY-4+, andreverse primer DLIANKY-2-, having the nucleotide sequence 5'GGAATTTGCGACGACGCGGTTC 3', denoted herein as SEQ ID NO:48, which wasdesigned to hybridize to nucleotides 76-97 of SEQ ID NO:11, i.e., about76-97 nucleotides downstream of the 5'-end of nDiAnk₆₀₀. This secondamplification produced a single predominant PCR product of about 1228bp, as viewed by separation on an agarose gel, denoted herein asnDiAnk₁₂₂₈. This PCR product was gel purified and subcloned into plasmidpCRII as described in Example 1A. The nucleotide sequence of nDiAnk₁₂₂₈was determined, and is presented herein as SEQ ID NO:14 (the codingstrand) and SEQ ID NO:16 (the complementary strand). The 97 nucleotideson the 3' end of nDiAnk₁₂₂₈ lined up with 100% identity to the 97nucleotides on the 5' end of nDiANK₆₀₀ (disclosed in Example 1C).

Translation of SEQ ID NO:14 yields a protein of about 409 amino acids,denoted herein as PDiAnk₄₀₉, the amino acid sequence of which ispresented in SEQ ID NO:15, assuming a first in-frame codon extendingfrom nucleotide 1 to nucleotide 3 of SEQ ID NO:14. The coding regionencoding PDiAnk₄₀₉ is presented herein as nDiAnk₁₂₂₇, which has thenucleotide sequence SEQ ID NO:17 (the coding strand) and SEQ ID NO:18(the complementary strand). The 32 amino acid residues on the C-terminalend of PDiAnk₄₀₉ lined up with 100% identity to the 32 amino acidresidues on the N-terminal end of PDiAnk₂₀₀ disclosed in Example 1C).PDiAnk₄₀₉ thus represents about 377 amino acids of new D. immitisankyrin amino acid sequence.

E. An additional ankyrin nucleic acid molecule of about 573 bp wasisolated by PCR from a D. immitis 48-hour L3 cDNA library, as follows.

An about 573-bp D. immitis ankyrin nucleic acid molecule was amplifiedby standard PCR from a D. immitis 48-hour L3 cDNA library constructed asdescribed in Example 1A using a primer designed according to ankyrinnucleic acid sequences of D. immitis, derived as described in Example1D, and an M13 reverse primer. The primers included forward primer M13reverse, having the nucleotide sequence 5' CAGGAAACAGCTATGAC 3', denotedherein as SEQ ID NO:49 and reverse primer DIANKY-3-, having thenucleotide sequence 5' TGGAGTTTGTCCTGTCGATGTATG 3', denoted herein asSEQ ID NO:50. DIANKY-3- was designed to hybridize to nucleotides 73-96of SEQ ID NO:14, i.e., about 73-96 nucleotides downstream of the 5'-endof nDiAnk₁₂₂₈. A PCR product of about 573 bp was observed upon agarosegel electrophoresis of the PCR reaction, which is denoted herein asnDiAnk₅₇₃. The PCR product was gel purified and subcloned into the pCRIIvector as described in Example 1A. The nucleotide sequence of nDiAnk₅₇₃was determined, and is presented herein as SEQ ID NO:19 (the codingstrand) and SEQ ID NO:21 (the complementary strand). The 96 nucleotideson the 3' end of nDiAnk₅₇₃ lined up with 100% identity to the 96nucleotides on the 5' end of nDiANK₁₂₂₈ (disclosed in Example 1D).

Translation of SEQ ID NO:19 yields a protein of about 191 amino acids,denoted herein as PDiAnk₁₉₁, the amino acid sequence of which ispresented in SEQ ID NO:20, assuming a first in-frame codon extendingfrom nucleotide 1 to nucleotide 3 of SEQ ID NO:19. The 32 amino acidresidues on the C-terminal end of PDiAnk₁₉₁ lined up with 100% identityto the 32 amino acid residues on the N-terminal end of PDiAnk₄₀₉(disclosed in Example 1D). PDiAnk₁₉₁ thus represents approximately 159amino acids of new D. immitis ankyrin amino acid sequence.

F. An additional ankyrin nucleic acid molecule of about 911 bp wasisolated from first-strand reverse transcriptase cDNA syntheses of D.immitis adult messenger RNA by PCR, as follows.

Attempts to isolate additional portions of a D. immitis ankyrin nucleicacid molecule from a cDNA library were unsuccessful. Therefore,additional portions were isolated from first-strand reversetranscriptase cDNA syntheses of D. immitis adult messenger RNA, by PCRamplification. A D. immitis-specific reverse primer was designed nearthe 5' terminus of nDiAnk₅₇₃ described in Example 1E above. This primer,denoted as DIANKY-4-, having the nucleotide sequence 5'GCTTTGCTTTCAGCATTCGCATTTGCC 3', denoted herein as SEQ ID NO:5 1, alongwith degenerate forward primer CEANKY-4+, described in Example 1D, wereused in PCR amplifications of first-strand reverse transcriptase cDNAsyntheses of D. immitis adult messenger RNA, prepared by standardmethods. DIANKY-4- was designed to hybridize to nucleotides 138-164 ofSEQ ID NO:19, i.e., about 138-164 nucleotides downstream of the 5'-endof nDiAnk₅₇₃. A PCR product of about 911 bp, visualized by agarose gelelectrophoresis, was obtained by PCR amplification using as a templatefirst strand cDNA syntheses of either adult female or adult male D.immitis messenger RNA using these primers. It should be noted that PCRamplifications performed with three other degenerate forward primers,designed from the UNC-44 nucleotide sequence of Otsuka, et al., ibid.,in conjunction with D. immitis reverse primers, did not result in thesuccessful amplification of D. immitis ankyrin nucleic acid molecules.The 911-bp PCR products were excised from the agarose gel on which theywere separated, and bathed in a small volume of Tris-EDTA buffer. Tenmicroliter aliquots of these excised products in TE were used astemplate for reamplification PCRs, using the same primers, to verify theproduct. More intense bands of exactly the same size, denoted herein asnDiAnk₉₁₁, were produced by these second round PCRs, as seen byseparation on an agarose gel.

Nucleic acid molecules from both the first and second PCR reactions weregel purified and subcloned into plasmid pCRII as described in Example1A. The subcloned DNA products were submitted for automated sequencing.Sequence analysis revealed that the inserts of all PCR products wereidentical, and are denoted herein as SEQ ID NO:22 (the coding strand)and SEQ ID NO:24 (the complementary strand). The 164 nucleotides on the3' end of nDiAnk₉₁₁ lined up with 100% identity to the 164 nucleotideson the 5' end of nDiANK₅₇₃ (disclosed in Example 1E).

Translation of SEQ ID NO:22 yields a protein of about 303 amino acids,denoted herein as PDiAnk₃₀₃, the amino acid sequence of which ispresented in SEQ ID NO:23, assuming a first in-frame codon extendingfrom nucleotide 1 to nucleotide 3 of SEQ ID NO:22. The coding regionencoding PDiAnk₃₀₃ is presented herein as nDiAnk₉₀₉, which has thenucleotide sequence SEQ ID NO:25 (the coding strand) and SEQ ID NO:26(the complementary strand). The 54 amino acid residues on the C-terminalend of PDiAnk₃₀₃ lined up with 100% identity to the 54 amino acidresidues on the N-terminal end of the PDiAnk₁₉₁ (disclosed in Example1E). PDiAnk₃₀₃ thus represents approximately 249 amino acids of new D.immitis ankyrin amino acid sequence.

G. An additional ankyrin nucleic acid molecule of about 1096 bp,containing sequences representing the authentic 5' end of a D. immitisankyrin messenger RNA, was isolated from first-strand reversetranscriptase cDNA syntheses of D. immitis adult messenger RNA by PCR,as follows.

A D. immitis-specific reverse primer was designed near the 5' terminusof nDiAnk₉₁₁ described in Example 1F above. This primer, denotedDIANKY-7-, having the nucleotide sequence 5' GTGAGATAGTCAACAGTAACATCATCC3', denoted herein as SEQ ID NO:53, was designed to hybridize tonucleotides 3-29 of SEQ ID NO:22, i.e., about 3-29 nucleotidesdownstream of the 5'-end of nDiAnk₉₁,. DIANKY-7- was used along with asense primer designed according to the nematode splice leader (SL) inPCR amplifications of first-strand reverse transcriptase cDNA synthesesof D. immitis adult messenger RNA, prepared by standard methods. Most,but not all nematode messenger RNAs have the SL at their 5' ends, andthe presence of the 5' SL sequence is indicative of an apparently fulllength cDNA molecule. See, for example Blaxter and Liu, 1996, Int. J.Parasitol. 26, 1025-1033, which is herein incorporated by reference inits entirety. The splice leader primer, denoted DiSL, has the nucleotidesequence 5' GGTTTAATTACCCAAGTTTGAG 3', denoted herein as SEQ ID NO:52.Using these primers, PCR products of about 1096 bp were obtained usingadult male and adult female mRNAs as templates. These nucleic acidmolecules were gel-purified using the QIAquick™ kit as permanufacturer's instructions. The yield of these purifications was low,so one microliter each of the purified DNA products were used astemplates in reamplification PCRs using the same primers. More intenseproducts of precisely the same size, collectively denoted herein asnDiANK₁₀₉₆, were obtained from the reamplification PCRs, and weresubcloned into plasmid pCRII as described in Example 1A. One of thesubcloned nucleic acid molecules was submitted for automated nucleicacid sequencing. Sequence analysis suggested that nDiAnk₁₀₉₆, thesequence of which is represented herein as SEQ ID NO:27 (the codingstrand) and SEQ ID NO:29 (the complementary strand), represented theauthentic 5' end of a D. immitis ankyrin messenger RNA. The 5' end ofnDiAnk₁₀₉₆ included the spliced leader sequence, 28 nucleotides of 5'untranslated sequence, and the starting methionine of the codingsequence. The 29 nucleotides on the 3' end of nDiAnk₁₀₉₆ lined up with100% identity to the 29 nucleotides on the 5' end of nDiANK₉₁₁(disclosed in Example 1F).

Translation of SEQ ID NO:27 yields a protein of about 348 amino acids,denoted herein as PDiAnk₃₄₈, the amino acid sequence of which ispresented in SEQ ID NO:28, assuming a start codon extending fromnucleotide 51 to nucleotide 53 of SEQ ID NO:27. The nucleic acidmolecule representing the coding region encoding PDiAnk₃₄₈, denotedherein as nDiAnk₁₀₄₄, is presented herein as SEQ ID NO:30 (the codingstrand) and SEQ ID NO:31 (the complementary strand). The about 9 aminoacid residues on the C-terminal end of PDiAnk₃₄₈ lined up with about100% identity to the about 9 amino acid residues on the N-terminal endof the PDiAnk₃₀₃ (disclosed in Example 1F). PDiAnk₃₄₈ thus representsapproximately 339 amino acids of new D. immitis ankyrin amino acidsequence.

H. A composite nucleotide sequence of a full-length D. immitis ankyringene was compiled as follows.

A D. immitis ankyrin nucleic acid molecule of 5503 bp, denoted herein asnDiAnk₅₅₀₃, including an apparently full-length coding region, wascompiled by aligning the overlapping nucleic acid sequences SEQ ID NO:1,SEQ ID NO:6, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:19, SEQ ID NO:22, andSEQ ID NO:27. The composite full-length nucleic acid molecule has anucleic acid sequence presented herein as SEQ ID NO:32 (the codingstrand) and SEQ ID NO:34 (the complementary strand). SEQ ID NO:32contains the 5' nematode spliced leader sequence extending from aboutnucleotide 1 through about nucleotide 27, and a 28 bp 5' non-codingregion extending from about nucleotide 28 through about nucleotide 50.

Translation of SEQ ID NO:32 yields a full-length protein of about 1745amino acids, denoted PDiAnk₁₇₄₅, assuming a start codon extending fromnucleotide 51 through nucleotide 53 of SEQ ID NO:32, and a stop codonextending from nucleotide 5286 through nucleotide 5285 of SEQ ID NO:32.The resulting amino acid sequence is presented as SEQ ID NO:33. Thecoding region encoding PDiAnk₁₇₄₅, not including the termination codonis denoted herein as nDiANK₅₂₃₅, and has the nucleotide sequence SEQ IDNO:35 (the coding strand) and SEQ ID NO:36 (the complementary strand).SEQ ID NO:35 is predicted to encode a protein with a molecular mass ofabout 191.7 kD and with a predicted pI of about 5.76, as calculated bythe DNAsis program.

A homology search of a non-redundant protein database was performed withSEQ ID NO:33, using the blastp program available through the BLAST™network of the National Center for Biotechnology Information (NCBI)(National Library of Medicine, National Institutes of Health, Baltimore,Md.), available on the World Wide Web. This database includesSwissProt+PIR+SPupdate+GenPept+GPUpdate+PDB databases. The highestscoring match of the homology search at the amino acid level wasGenBank™ accession number gi|1208874, a C. elegans ankyrin-like protein,to which SEQ ID NO:33 showed about 69% identity, spanning from aboutamino acid 1 through about amino acid 1745 of SEQ ID NO:33. The secondhighest scoring match of the homology search at the amino acid level wasGenBank™ accession number gi|406288, a human brain ankyrin protein(variant I, Ankyrin_(B)), to which SEQ ID NO:33 showed about 51%identity, spanning from about amino acid 1 through about amino acid1745. SEQ ID NO:33 was also compared to the sequence of the O. volvulusE1 protein as disclosed by Erttmann, et al., 1996a, ibid. A region ofSEQ ID NO:33 spanning from about amino acid 1282 to about amino acid1745 showed about 78% identity to the full-length O. volvulus E1 proteinof 467 amino acids. At the nucleotide level, the coding regionrepresented in SEQ ID NO:35 was compared to the cDNA encoding the O.volvulus E1 protein. A region of SEQ ID NO:35 spanning from aboutnucleotide 3423 to about nucleotide 5574 showed about 88% nucleic acididentity to the cDNA containing a full-length coding region of 1401nucleotides encoding the O. volvulus E1 protein.

Example 2

This Example discloses an analysis of the predicted functional domainsof a full-length D. immitis ankyrin protein.

Based on comparisons with mammalian ankyrin proteins, as well as theprotein encoded by the C. elegans UNC-44 gene, the putative positions ofthe three functional domains of ankyrin proteins were identified in SEQID NO:33, the amino acid sequence of an apparent full-length D. immitisankyrin protein, namely PDiAnk₁₇₄₅, isolated as disclosed in Example 1.While not being bound by theory, an N-terminal membrane protein-bindingdomain is predicted to extend from about amino acid 1 to about aminoacid 880 of SEQ ID NO:33, a spectrin-binding domain is predicted toextend from about amino acid 881 to about amino acid 1398 of SEQ IDNO:33, and a regulatory domain is predicted to extend from about aminoacid 1399 to about amino acid 1745 of SEQ ID NO:33.

The N-terminal membrane protein-binding domain of PDiAnk₁₇₄₅ is furthercharacterized by the presence of 24 tandemly arrayed repeats, most ofwhich comprise about 33 amino acid residues. These repeat regions arelisted in Table 1, designated by numbers, along with a general consensussequence pattern. The terms "start" and "end" in Table 1 refer to thesequential amino acid numbers in SEQ ID NO:33 corresponding to the firstand last amino acid, respectively, of each repeat listed in Table 1. Thefirst and the twenty-fourth repeats are not as well conserved as theother repeats. To the inventor's knowledge, this is the first disclosureof ankyrin-like repeats in a parasitic nematode.

                  TABLE 1                                                         ______________________________________                                        Ankyrin-like repeats of PDiAnk1745                                              No.   START                            END                                  ______________________________________                                        01  36      ESSASFLRAA RAGNLDRVLE LLRSGTDINT CNA                                                                      68                                       - 02  69    NGLNALHLAS KEGHHEVVRE LLKRKADVDA ATR   101                        - 03  102   KGNTALHIAS LAGQELIVTV LVENGANVNV QSL   134                        - 04  135   NGFTPLYMAA QENHESVVRY LLAHNANQAL STE   167                        - 05  168   DGFTPLAVAL QQGHDRVVAV LLENDTRGK˜ ˜˜.about                                           .   196                                   - 06  197   VRLPALHIAA KKDDTKAATL LLQNEHNSDV TSK   229                        - 07  230   SGFTPLHIAA HYGNENVAQL LLEKGANVNY QAR   262                        - 08  263   HNISPLHVAT KWGRTNMVSL LLAHGAVIDC RTR   295                        - 09  296   DLLTPLHCAS RSGHDQVVDL LLEKGAPISA KTK   328                        - 10  329   NGLAPLHMAA Q˜˜˜˜˜˜.abou                                           t.˜˜ ˜˜.abo                                           ut.˜˜˜˜VDD                                            VTV   345                                 - 11  346   DYLTPLHVAA HCGHVRVAKL LLDRNADPNA RAL   378                        - 12  379   NGFTPLHIAC KKNRIKIVEL LLKYHAAIEA TTE   411                        - 13  412   SGLSPLHVAA FMGAINIVIY LLQQGANADV ATV   444                        - 14  445   RGETPLHLAA RANQTDIVRV LVRNGAQVDA AAR   477                        - 15  478   ELQTPLHIAS RLGNTDIVIL LLQANASPNA ATR   510                        - 16  511   DLYTPLHIAA KEGQEEVAAI LMDHGTDKTL LTK   543                        - 17  544   KGFTPLHLAA KYGNLPVAKS LLERGTPVDI EGK   576                        - 18  577   NQVTPLHVAA HYNNDKVALL LLENGASAHA AAK   609                        - 19  610   NGYTPLHIAA KKNQMDIAST LLHYKANANA ESK   642                        - 20  643   AGFTPLHLAA QEGHREMAAL LIENGAKVGA QAR   675                        - 21  676   NGLTPMHLCA QEDRVSVAEE LVKENAAJDP KTK   708                        - 22  709   AGYTPLHVAC HFGQINMVRF LIEHGARVSV ITR   741                        - 23  742   ASYTPLHQAA QQGHNSVVRY LLEHGASPNV HTS   774                        - 24  775   TGQTPLSIAE RLGYVSVVEA LKTITETTVI TET   807                     Consensus                                                                     G-TPLH-AA--GH---V                                                             -- LL--GA--N- ---                                                                                  A           D                                            ______________________________________                                    

Repeat regions 01 through 24 as disclosed in Table 1 are presentedherein as SEQ ID NO:61 through SEQ ID NO:84, respectively. The consensussequence is presented herein as SEQ ID NO:85. A novel feature of themembrane-binding domain of PDiAnk₁₇₄₅ is repeat No. 10 (SEQ ID NO:70),which apparently comprises only 17 amino acids. While not being bound bytheory, this shortened repeat is unique among ankyrin proteins.

Example 3

This Example demonstrates the use of D. immitis nucleic acid moleculesof the present invention to obtain, by PCR amplification, an ankyrinnucleic acid molecule from a related filariid nematode, Brugia malayi.

A B. malayi ankyrin nucleic acid molecule was PCR amplified from afirst-strand cDNA synthesis of messenger RNA prepared from B. malayiadult female worms, as follows. The PCR primers included forward primerCEANKY 4+, as disclosed in Example 1D, and reverse primer DIANKY 4-, asdisclosed in Example 1F. An about 908-bp nucleic acid molecule wasamplified in a PCR amplification of a first-strand reverse transcriptasecDNA synthesis of B. malayi adult female messenger RNA, prepared bystandard methods, and is herein denoted as nBmAnk₉₀₈.

Nucleic acid molecule nBmAnk₉₀₈ was gel purified and subcloned intoplasmid pCRII, and sequenced as described in Example 1A. The sequence ispresented as SEQ ID NO:37 (the coding strand) and SEQ ID NO:39 (thecomplementary strand). Translation of SEQ ID NO:37 yields anon-full-length protein of about 302 amino acids, herein denoted asPBmAnk₃₀₂, assuming a first in-frame codon extending from nucleotide 1through nucleotide 3 of SEQ ID NO:37. The resulting amino acid sequenceis presented as SEQ ID NO:38. The coding region encoding PBmAnk₃₀₂ isherein denoted as nBmANK₉₀₆, and has the nucleotide sequence SEQ IDNO:40 (the coding strand) and SEQ ID NO:41 (the complementary strand).

A homology search of a non-redundant protein database was performed onSEQ ID NO:38 using the BLAST network. The homology spans from aboutamino acid 1 through amino acid 302 of SEQ ID NO:38. The highest scoringmatch of the homology search at the amino acid level was GenBankaccession number A57282, a C. elegans ankyrin-like protein, which wasabout 86% identical to SEQ ID NO:38 through a region extending fromabout amino acid 353 through about amino acid 654 of A57282. The B.malayi ankyrin nucleic acid molecule and protein sequences representedby SEQ ID NO:37 and SEQ ID NO:38, respectively, had no similarity to theO. volvulus E1 nucleic acid molecule and protein disclosed by Erttmann,et al., 1996a, ibid.

The amino acid sequence of SEQ ID NO:38 was also compared to PDiAnk₁₇₄₅(i.e., SEQ ID NO:33 of the present invention). PBmAnk₃₀₂ had 95%identity to the region of SEQ ID NO:33 spanning from about amino acid341 through about amino acid 642.

Example 4

The following experiment was performed in order to confirm the origin ofthe ankyrin gene in the D. immitis genome, and to identify genomicrestriction fragments associating with a partial ankyrin cDNA clone. Theexperiment also evaluates if multiple copies of the ankyrin gene arepresent in the D. immitis genome. Four enzymes were each usedindividually to digest about 10 micrograms of D. immitis genomic DNAeach. A Southern blot containing genomic DNA samples restricted withSau3A-I, EcoRI, HindIII, and XhoI, respectively, was hybridized understringent conditions using nDiAnk₉₃₇, isolated as disclosed in Example1A, labeled with the radioactive isotope ³² P. The nDiAnk₉₃₇ probehybridized to three bands of 460 bp, 550 bp, and 770 bp in the genomicrestriction digestion using Sau3A-I. A single band of 5490 bp hybridizedin the EcoRI digestion. Two bands of 930 bp and 3330 bp hybridized inthe HindIII digestion. Two bands also hybridized in the XhoI digestion(which of the four enzymes digested the genomic DNA most incompletely),one of 3330 bp and one of 43,200 bp, the latter appearing in a bandrepresenting undigested DNA. This experiment confirmed the D. immitisorigin of ankyrin nucleic acid molecules of the present invention. Whilenot being bound by theory, since no EcoRI sites are present within thefull-length coding region of nDiAnk₁₇₄₅, the single EcoRI genomicfragment hybridizing with the nDiAnk₉₃₇ probe suggests that at least theportion of nDiAnk₁₇₄₅ included in nDiAnk₉₃₇ is present as a single copyin the D. immitis genome.

Example 5

This Example discloses the production of a recombinant molecule and arecombinant cell of the present invention.

Recombinant molecule pTrc-nDiAnk₁₈₆₆, containing a D. immitis ankyrinnucleic acid molecule operatively linked to trc transcription controlsequences and to a fusion sequence encoding the T7 tag and apoly-histidine segment, was produced in the following manner. An about1866-nucleotide DNA fragment containing nucleotides spanning from about3423 through about 5288 of SEQ ID NO:32, herein denoted as nDiAnk₁₈₆₆,was PCR-amplified by "touchdown" PCR from D. immitis L3 and LA cDNAlibraries produced by the methods described in Example 1A, using senseprimer OVANKY 1+ (SEQ ID NO:44, as described in Example 1C), andDIANKY-, having the nucleotide sequence 5'CCGGAATTCTTATTCATGAACGCTTTGCCCTTT 3', herein denoted as SEQ ID NO:55,EcoRI site in bold. DIANKY- was designed to anneal to a region of SEQ IDNO:32 extending from nucleotide 5365 through nucleotide 5288. This PCRproduct was gel-purified using the QIAquick™ kit as per manufacturer'sinstructions. The yield of this purification was low, so one microliterof the purified DNA product was used as template in a reamplificationPCR (standard PCR) using forward primer DIANKY 3+, having the nucleotidesequence 5' CGCGGATCCGGCACAACCAGTTCCGCAAGAA 3', herein denoted as SEQ IDNO:54, BamHI site in bold, and antisense primer DIANKY-, as describedabove. DIANKY 3+ was designed to anneal to the PCR product generatedabove, but shares 17/20 bp in common with nucleotides 3423 through 3443of SEQ ID NO:32. A more intense product of approximately the same size,denoted herein as nDiAnk₁₈₆₆, was obtained from the reamplification PCR.Recombinant molecule pTrc-nDiAnk₁₈₆₆ was produced by digesting thePCR-amplified DNA fragment with BamHI and EcoRI restrictionendonucleases, gel purifying the resulting fragment and directionallysubcloning it into expression vector pTrcHisB (available fromInvitrogen) that had been cleaved with BamHI and EcoRI and gel purified.

Recombinant molecule pTrc-nDiAnk₁₈₆₆ was transformed into E. coli toform recombinant cell E. coli:pTrc-nDiAnk₁₈₆₆ using standard techniques.

Example 6

This Example discloses the production of additional recombinantmolecules and recombinant cells of the present invention. Also describedis an analysis of the nucleic acid sequence encoding each of the threedomains described above, as well as an analysis of the amino acidsequence of each.

A. Recombinant molecule pTrc-nDiAnk₁₀₅₆, containing a D. immitis ankyrinnucleic acid molecule encoding the predicted membrane protein-bindingdomain (disclosed in Example 2), operatively linked to trc transcriptioncontrol sequences and to a fusion sequence encoding the T7 tag and apoly-histidine segment, was produced in the following manner. An about1056-nucleotide DNA fragment spanning from about nucleotide 1356 throughabout nucleotide 2411 of SEQ ID NO:32, denoted herein as nDiAnk₁₀₅₆, wasRT-PCR-amplified from four different D. immitis messenger RNA templates.The templates were as follows: 48-hour L3 (i.e., third-stage larvaeharvested at 48 hours), 6-day L4 (i.e., fourth stage larvae harvested at6 days), adult female, and adult male D. immitis mRNAs. The PCR primersincluded DIANKY REP+, having the nucleotide sequence 5'CGCGGATTCGCGCGGTGCTAATGCAGATGTGGC 3', denoted herein as SEQ ID NO:56,BamHI site in bold, and reverse primer DIANKY REP-, having thenucleotide sequence 5' CCGGAATTCCGGTTACCCTAGACGTTCAGCAATCG 3', denotedherein as SEQ ID NO:57, EcoRI site in bold. The amplification produced aproduct of the predicted size from each of the four mRNA templates. Thisresult indicates that the portion of the D. immitis ankyrin geneencoding the putative membrane protein-binding domain is expressed in atleast two larval stages and in male and female adult parasites.Recombinant molecule pTrc-nDiAnk₁₀₅₆ was produced by BamHI and EcoRIrestriction endonuclease digesting the PCR-amplified DNA fragmentsproduced using the 48-hour L3 D. immitis mRNA as the template, gelpurifying the resulting fragment and directionally subcloning it intoexpression vector pTrcHisB (available from Invitrogen) which was cleavedwith BamHI and EcoRI and gel purified.

The nucleic acid molecule encoding the N-terminal membraneprotein-binding domain, referred to herein as nDiAnk₁₀₅₆ (the nucleicacid sequence of the coding and non-coding strands of which are hereinreferred to as SEQ ID NO:138 and SEQ ID NO:140, respectively) encodes a352 amino acid sequence herein referred to as SEQ ID NO:139. A homologysearch of a non-redundant protein database was performed with SEQ IDNO:139, using the blastp program available through the BLAST198 networkof the NCBI, as described above. The highest scoring match of thehomology search at the amino acid level was to GenBank™ accession numberpir∥A57282, a C. elegans ankyrin-related protein fragment, UNC-44, towhich SEQ ID NO:139 showed about 80% identity, spanning from about aminoacid 1 through about amino acid 352 of SEQ ID NO:139. The highestscoring match of a homology search at the nucleotide level was to anucleotide sequence encoding C. elegans ankyrin-related protein,GenBank™ accession number gb|U21734|CEU21734. A region of SEQ ID NO:138spanning from about nucleotide 1 through about nucleotide 263 was foundto share about 71% identity with a region of gb|U21734|CEU21734 spanningfrom nucleotide 4126 to nucleotide 4388. In addition, a region of SEQ IDNO:138 spanning from about nucleotide 262 through about nucleotide 896was found to share about 68% identity with a region ofgb|U21734|CEU21734 spanning from nucleotide 4743 to nucleotide 5377.

B. Recombinant molecule pTrc-nDiAnk₁₂₆₆, containing a D. immitis ankyrinnucleic acid molecule encoding the predicted spectrin-binding domain(disclosed in Example 2), operatively linked to trc transcriptioncontrol sequences and to a fusion sequence encoding the T7 tag and apoly-histidine segment, was produced in the following manner. An about1266-nucleotide DNA fragment spanning from about nucleotide 2850 throughabout nucleotide 4115 of SEQ ID NO:32, denoted herein as nDiAnk₁₂₆₆, wasRT-PCR-amplified from the four different D. immitis messenger RNAtemplates described in Example 6A above. The PCR primers included DIANKYSPECT B+, having the nucleotide sequence 5'CCGGGATCCGCGCGCACGTGGAGGAGCAATGCGT 3', denoted herein as SEQ ID NO:58,BamHI site in bold, and reverse primer DIANKY SPECT B-, having thenucleotide sequence 5' CGCGAATTCCGGTTATTCGTTGTCCGTGTGAGTGCG 3', denotedherein as SEQ ID NO:59, EcoRI site in bold. The amplification produced aproduct of the predicted size from each of the four mRNA templates. Thisresult indicates that the portion of the D. immitis ankyrin geneencoding the putative spectrin-binding domain is expressed in at leasttwo larval stages and in male and female adult parasites. Recombinantmolecule pTrc-nDiAnk₁₂₆₆ was produced by BamHI and EcoRI restrictionendonuclease digesting the PCR-amplified DNA fragments produced usingthe 48-hour L3 D. immitis mRNA as the template, gel purifying theresulting fragment and directionally subcloning it into expressionvector pTrcHisB (available from Invitrogen) which was cleaved with BamHIand EcoRI and gel purified.

The nucleic acid molecule encoding the predicted spectrin-bindingdomain, referred to herein as nDiAnk₁₂₆₆ (the nucleic acid sequence ofthe coding and non-coding strands of which are herein referred to as SEQID NO:141 and SEQ ID NO:143, respectively) encodes a 422 amino acidsequence herein referred to as SEQ ID NO:142. A homology search of anon-redundant protein database was performed with SEQ ID NO:142, usingthe blastp program available through the BLAST™ network of the NCBI, asdescribed above. The highest scoring match of the homology search at theamino acid level was to GenBank™ accession number gi|1208873, a C.elegans ankyrin-related protein, to which SEQ ID NO:142 showed about 90%identity, spanning from about amino acid 1 through about amino acid 422of SEQ ID NO:142. The highest scoring match of a homology search at thenucleotide level was to a nucleotide sequence encoding C. elegansankyrin-related protein fragment, UNC-44, GenBank™ accession numbergb|U21732|CEU21732. A region of SEQ ID NO:141 spanning from aboutnucleotide 1 through about nucleotide 1266 was found to share about 73%identity with a region of gb|U21732|CEU21732 spanning from nucleotide337 to nucleotide 1602.

C. Recombinant molecule pTrc-nDiAnk₈₆₄, containing a D. immitis ankyrinnucleic acid molecule encoding the predicted regulatory domain(disclosed in Example 2), operatively linked to trc transcriptioncontrol sequences and to a fusion sequence encoding the T7 tag and apoly-histidine segment, was produced in the following manner. An about864-nucleotide DNA fragment spanning from about nucleotide 4425 throughabout nucleotide 5288 of SEQ ID NO:32, denoted herein as nDiAnk₈₆₄, wasRT-PCR-amplified from the four different D. immitis messenger RNAtemplates described in Example 6A above. The PCR primers included DIANKYREG+, having the nucleotide sequence 5'CGCGGATCCGCGCCAACTAGTTGGTCTTGAAGCAGTC 3', denoted herein as SEQ IDNO:60, BamHI site in bold, and reverse primer DIANKY-, having thenucleotide sequence 5' CCGGAATTCTTATTCATGAACGCTTTGCCCTTT 3', denotedherein as SEQ ID NO:55, EcoRI site in bold. The amplification produced aproduct of the predicted size from each of the four mRNA templates. Thisresult indicates that the portion of the D. immitis ankyrin geneencoding the putative regulatory domain is expressed in at least twolarval stages and in male and female adult parasites. Recombinantmolecule pTrc-nDiAnk₈₆₄ was produced by BamHI and EcoRI restrictionendonuclease digesting the PCR-amplified DNA fragments produced usingthe 48-hour L3 D. immitis mRNA as the template, gel purifying theresulting fragment and directionally subcloning it into expressionvector pTrcHisB (available from Invitrogen) which was cleaved with BamHIand EcoRI and gel purified.

The nucleic acid molecule encoding the N-terminal membraneprotein-binding domain, referred to herein as nDiAnk₈₆₄ (the nucleicacid sequence of the coding and non-coding strands of which are hereinreferred to as SEQ ID NO:144 and SEQ ID NO:146, respectively) encodes a864 amino acid sequence herein referred to as SEQ ID NO:145. A homologysearch of a non-redundant protein database was performed with SEQ IDNO:145, using the blastp program available through the BLAST™ network ofthe NCBI, as described above. The highest scoring match of the homologysearch at the amino acid level was to GenBank™ accession numbergnl|PID|e2791, the O. volvulus E1 protein, to which SEQ ID NO:145 showedabout 75% identity, spanning from about amino acid 1 through about aminoacid 108 of SEQ ID NO:145. The highest scoring match of a homologysearch at the nucleotide level was to an mRNA sequence encoding the O.volvulus E1 protein, GenBank™ accession number emb|X84359|OVMRNAANH. Aregion of SEQ ID NO:144 spanning from about nucleotide 1 through aboutnucleotide 367 was found to share about 84% identity with a region ofemb|X84359|OVMRNAANH spanning from nucleotide 996 to nucleotide 1362. Inaddition, a region of SEQ ID NO:144 spanning from about nucleotide 358through about nucleotide 498 was found to share about 95% identity witha region of emb|X84359|OVMRNAANH spanning from nucleotide 1350 tonucleotide 1490.

Recombinant molecules pTrc-nDiAnk₁₀₅₆, pTrc-nDiAnk₁₂₆₆, andpTrc-nDiAnk₈₆₄ were transformed into E. coli to form recombinant cellsE. coli:pTrc-nDiAnk₁₀₅₆, E. coli:pTrc-nDiAnk₁₂₆₆, and E.coli:pTrc-nDiAnk₈₆₄ using standard techniques.

Example 7

This example demonstrates the production of D. immitis ankyrin proteinsof the present invention in prokaryotic cells.

Recombinant cell E. coli:pTrc-nDiAnk₁₈₆₆, produced as described inExample 5, was cultured in shake-flasks containing an enriched bacterialgrowth medium containing 0.1 mg/ml ampicillin at about 37° C. When thecells reached an OD₆₀₀ of about 0.5, expression of D. immitis nucleicacid molecule nDiAnk₁₈₆₆ was induced by addition of about 0.5 mM IPTG,and the cells were cultured for about 3 hr at about 37° C. Proteinproduction was monitored by SDS-polyacrylamide gel electrophoresis(SDS-PAGE) of recombinant cell lysates, followed by Coomassie bluestaining, using standard techniques. Recombinant cell E.coli:pTrc-nDiAnk₁₈₆₆ produced a fusion protein, denoted herein asPHIS-PDiANK₆₂₂, that migrated with an apparent molecular weight of about98 kD, although the predicted molecular weight is only about 74 kD.While not being bound by theory, the difference between the observed andpredicted molecular weights may be attributed to the known acidity ofthe regulatory domains of ankyrin proteins, which is known by thoseskilled in the art to reduce the binding of SDS to the protein, therebyresulting in an aberrant migration in SDS-PAGE.

Immunoblot analysis of recombinant cell E. coli:pTrc-nDiAnk₁₈₆₆ lysatesindicated that the about 98-kD protein was able to bind to a T7 tagmonoclonal antibody (available from Novagen, Inc., Madison, Wis.)directed against the fusion portion of the recombinant PHIS-PDiANK₆₂₂fusion protein.

Recombinant cells E. coli:pTrc-nDiAnk₁₀₅₆, E. coli:pTrc-nDiAnk₁₂₆₆, andE. coli:pTrc-nDiAnk₈₆₄, produced as described above, were culturedseparately in shake-flasks containing an enriched bacterial growthmedium containing 0.1 mg/ml ampicillin at about 37° C. When the cellsreached an OD₆₀₀ of about 0.5, expression of D. immitis nucleic acidmolecules nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, and nDiAnk₈₆₄, respectively, wasinduced by addition of about 0.5 mM IPTG, and the cells were culturedfor about 3 hr at about 37° C. Protein production was monitored bySDS-PAGyacrylamide gel electrophoresis (SDS-PAGE) of recombinant celllysates, followed by Coomassie blue staining, using standard techniques.Recombinant cells E. coli:pTrc-nDiAnk₁₀₅₆, E. coli:pTrc-nDiAnk₁₂₆₆, andE. coli:pTrc-nDiAnk₈₆₄, produced fusion proteins denoted herein asPHIS-PDiANK₃₅₂, PHIS-PDiANK₄₂₂, and PHIS-PDiANK₂₈₈, respectively.

Example 8

This example discloses the purification of the D. immitis ankyrinmembrane protein-binding fusion protein, the D. immitis ankyrinspectrin-binding domain fusion protein, and the D. immitis regulatorydomain fusion protein. The designation and expression of each domain aredescribed herein. Also described is the production of antibodiesdirected against the fusion proteins of each domain, respectively.

The procedures for purifying the fusion proteins representing each ofthe different domains (PHIS-PDiANK₃₅₂, PHIS-PDiANK₄₂₂, andPHIS-PDiANK₂₈₈) were essentially the same for each, and were as follows.E. coli expressed fusion protein was separated from other proteins bymetal ion affinity chromatography. The soluble portion of the proteinwas suspended in 1× PBS and applied to a 1 ml HiTrap Chelating column(available from Pharmacia Biotech, Piscataway, N.J.) charged with nickel(Ni⁺⁺) ions. The purification scheme was performed using standard FPLCtechniques utilizing the BioRad Biologic Chromatography System(available from BioRad Laboratories, Hercules, Calif.). The fusionprotein was eluted using an imidazole gradient. Fractions collectedfollowing separation were analyzed by separation on SDS-PAGE gels, anddetected by Coomassie Blue staining and Western blotting. Immunoblottingwas performed using standard techniques for transfer to nitrocelluloseand fusion proteins were detected using a T7-tag Mab. FPLC fractionscontaining the fusion protein of interest were pooled and theconcentration of protein was determined by a BioRad Protein Assay(available from BioRad Laboratories).

Antisera to the three D. immitis ankyrin domains (the three antiseraalso referred to herein as rabbit anti-DiANK₃₅₂, rabbit anti-DiANK₄₂₂,and rabbit anti-DiANK₂₈₈, antisera, respectively) were produced asfollows: One rabbit for each fusion protein (3 total) was immunizedsubcutaneously with 50 μg of purified fusion protein in CompleteFreund's Adjuvant (available from Sigma, St. Louis, Mo.). Each rabbitwas boosted two times, using the same dose of fusion protein as was usedfor the original immunization, in Incomplete Freund's adjuvant, with twoweeks between immunizations. Serum samples were collected betweenimmunizations, and then every other week following the second boost.Serum from each bleed was stored separately at -20° C. until use.

Example 9

This example describes the identification of ankyrin antibodies in therabbit polyclonal antisera raised against each of the three D. immitisankyrin domains. Rabbit anti-DiANK₃₅₂, rabbit anti-DiANK₄₂₂, and rabbitanti-DiANK₂₈₈ antisera, produced as described above, were used toidentify the original E. coli fusion proteins used to immunize therespective rabbits. This was done to verify that antibodies against thefusion protein were indeed the major product of the immunization.

Each of the purified fusion proteins (representing each of thefunctional domains described above) was run on a 14% Tris-glycineSDS-PAGE gel for 2.5 hours at 150 V. Approximately 3 μg of protein wasrun per lane on the gel, and then transferred to a nitrocellulosemembrane by standard methods. Following transfer, the membranes wereblocked in 5% dry milk for one hour at room temperature. Each membranewas then incubated for one hour with antisera representing the threedomains. Each antisera was used at dilutions of 1:500 and 1:2000 in 1×TBST. Following appropriate washing, each membrane was incubated anotherone hour with an alkaline phosphatase labeled anti-rabbit secondaryantibody. Detection of protein was obtained using the substrate NBT/BCIP(Gibco BRL, Gaithersburg, Md.). Each antiserum identified thecorresponding fusion protein of the predicted size, which matches thesize of the recombinant protein originally used for immunization andpolyclonal antibody production.

Example 10

This example describes the isolation and sequencing of several D.immitis ankyrin genomic nucleic acid molecules from adult D. immitisgenomic DNA. As in the above examples describing the isolation ofankyrin cDNA molecules, some of the nucleic acid molecules disclosed inthis example were isolated by PCR with degenerate primers and/or primersnot fully identical to the D. immitis sequences. As described above, theauthentic D. immitis nucleotide sequences were verified on overlappingnucleic acid molecules, and thus the nucleotide sequences of the nucleicacid molecules disclosed in this example are fully representative of D.immitis genomic DNA sequences.

Genomic DNA was prepared from whole adult worms using standard DNAextraction methods, well known in the art. This genomic DNA was thenused as the template for "touchdown" PCR as described above. The newprimers used for amplification of genomic DNA were based on the nucleicacid sequence of D. immitis ankyrin nucleic acid molecule hereindisclosed. In addition, some of the primers used to amplify genomic DNAare described above, and had been used successfully to amplify D.immitis ankyrin cDNA nucleic acid sequences. These primers aresummarized in Table 2.

                  TABLE 2                                                         ______________________________________                                        Primer Loca-                                                                    tion re-                                                                      lative to                                                                     SEQ ID SEQ ID                                                                 NO:32         NO:   Primer                                                  ______________________________________                                         51-73 a 147     CGCGGATCCG CATGAGTAAT CCTATAGTCG                                                             AGGG                                             -  486-506 b        148   TACAACAGAT TCGTGATTTT C                             -  726-743 a        149   GTGACTTCGA AAAGCGGC                                 - 1070-1097 b      53    GTGAGATAGT CAACAGTAAC ATCATCC                        - 1356-1375 a      56    CGCGGATTCG CGCGGTGCTA ATGCAGATGT                                              GGC                                                  - 1952-1978 b      51    GCTTTGCTTT CAGCATTCGC ATTTGCC                        - 2133-2156 a      150   GAACTAGTGA AAGAAAACGC AGCC                           - 2292-23l4 b      151   GTAACGTACA ACACTGTTAT GCCC                           - 2310-2333 a      46    CAYCARGCNG CNCARCARGG NCA                            - 2392-2411 b     57    CCGGAATTCC GGTTACCCTA GACGTTCAGC                                               AATCG                                                - 2553-2576 a      152   GGTGAAGATA ATCAGATCAC AGCC                           - 2760-2780 b      153   CGATGCATCT AAGGAAGGAT C                              - 2760-2780 a      154   GATCCTTCCT TAGATGCATC G                              - 2886-2909 b      155   CGGTGGTATA ATGATTCTGA CACC                           - 2850-2870 a      58    CGCGGATCCG CGCGCACGTG GAGGAGCAAT                                              GCGT                                                 - 3078-3104 b      156   CTCTCTCTCT CGTCCACGAA GTGATGC                        - 4425-4448 a       60   CGCGGATCCG CGCCAACTAG TTGGTCTTGA                                               AGCAGTC                                             - 4896-4917 b      43    CGTTTACAGC AACATCATCC TC                             - 4824-4841 a       157   CGCACTGAAC GACATGTG                                 - 5040-5060 b      158   CTCATGTGTT GTCTGACAAC C                              - 5163-5183 a      159   GGATTAAGTA GCGGGGATGC A                              - 5319-5339 b      160   GCAACATAGG CATGTGCGAG A                           ______________________________________                                    

Table 2 lists the primers used for PCR amplification of D. immitisankyrin nucleic acid sequences from genomic DNA. Endonuclease cleavagesites added as linkers to some of the primers are noted in bold. "a" or"b" after the primer location designation denotes that the primercorresponds to the sense or antisense strand, respectively, of ankyrinDNA. Table 2 also lists the location of these primer sequences relativeto the sequence of full-length D. immitis ankyrin cDNA (SEQ ID NO:32,the coding strand; note that the location of the second member of eachprimer pair (denoted with the designation, "b") is also listed relativeto SEQ ID NO:32, although the sequence of these primers is the reversecomplement of the listed portion of SEQ ID NO:32).

Amplification with the primers listed in Table 2 was performed inparallel using genomic DNA as the template for one set of amplificationreactions, and cDNA (as described above) as the template in the parallelset of control amplification reactions. The amplification reactionproducts were detected by agarose gel electrophoresis, and the presenceof introns in genomic DNA fragments was detected by observing a shift inthe molecular weight of the genomic DNA amplification product relativeto the cDNA product produced with the same primers. The PCR-amplifiedfragments representing genomic DNA were excised from the gel andpurified as described above. The resultant DNA fragments were subcloned,as above, into the pCRII™ vector according to the manufacturer'sinstructions. Sequencing of these fragments was performed as describedabove.

Example 11

This Example describes ankyrin introns and exons, and provides ananalysis of the nucleic acid sequence encoding the exons and intronsdescribed above. Also included is an analysis of the amino acid sequenceof each exon.

Sequence analysis revealed the location and sequence of eleven exons inthe nucleic acid sequence encoding D. immitis ankyrin. By comparing theD. immitis ankyrin cDNA sequence with the genomic sequence, the size andsequence of these eleven exons have been identified.

                  TABLE 3                                                         ______________________________________                                        SEQ ID     Name/Location relative                                               NO: to SEQ ID NO:32 Designation                                             ______________________________________                                         86        Exon 51-152      DiAnk-ex.sub.102                                     88 Exon 153-353 DiAnk-ex.sub.201                                              90 Exon 848-1034 DiAnk-ex.sub.187                                             92 Exon 1035-1068 DiAnk-ex.sub.34                                             94 Exon 1464-1613 DiAnk-ex.sub.150                                            96 Exon 2212-2372 DiAnk-ex.sub.161                                            98 Exon 2825-2957 DiAnk-ex.sub.133                                           100 Exon 4495-4673 DiAnk-ex.sub.179                                           102 Exon 4674-4857 DiAnk-ex.sub.184                                           104 Exon 4858-5015 DiAnk-ex.sub.158                                           106 Exon 5230-5288 DiAnk-ex.sub.59                                          ______________________________________                                    

The eleven exons that have been fully sequenced, and their locationsrelative to SEQ ID NO:32 are listed in Table 3, as are theircorresponding SEQ ID NO:s. The exon name indicates the location of eachexon relative to the D. immitis cDNA sequence, SEQ ID NO:32 (i.e., thenucleotides in the cDNA sequence that represent the exon). The exondesignation includes as a subscript the size, in nucleotides, of theexon. The reverse complements of the nucleic acid sequences hereindenoted SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ IDNO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ IDNO:104, and SEQ ID NO:106, are herein denoted SEQ ID NO:87, SEQ IDNO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ IDNO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, and SEQ ID NO:107,respectively. The amino acid sequences encoded by nucleic acid SEQ IDNO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ IDNO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, andSEQ ID NO:106 are herein denoted SEQ ID NO:86, SEQ ID NO:88, SEQ IDNO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ IDNO:100, SEQ ID NO:102, SEQ ID NO:104, and SEQ ID NO:106, respectively.

A homology search of a non-redundant protein database was performed witheach of the listed exons, using the blastx program available through theBLAST™, using the default settings. The blastx sequence analysis programtranslates a nucleic acid sequence in all six possible reading frames,and compares the results from each translation with the sequences in thedatabase. The results of the blastx analysis is summarized as follows:Analysis of the amino acid sequence coded by SEQ ID NO:86 (hereindenoted SEQ ID NO:161) revealed no significant homologies. The highestscoring match for the protein encoded by SEQ ID NO:88 (herein denotedSEQ ID NO:162) was to GenBank™ accession number g|1208875, a C. elegansankyrin-related protein. Nucleotide 4 through about nucleotide 183 ofSEQ ID NO:88 encodes a protein that showed about 83% identity tog|1208875. The highest scoring match for the protein encoded by SEQ IDNO:90 (herein denoted SEQ ID NO:163) was to GenBank™ accession numbergi|1208776, a C. elegans ankyrin-related protein. Nucleotide 3 throughabout nucleotide 180 of SEQ ID NO:90 encodes a protein that showed about82% identity to gi|1208776. The highest scoring match for the proteinencoded by SEQ ID NO:92 (herein denoted SEQ ID NO:164) was to GenBank™accession number gi|1208776, a C. elegans ankyrin-related protein.Nucleotide 1 through nucleotide 33 of SEQ ID NO:92 encodes a proteinthat showed 100% identity to gi|1208776. The highest scoring match forthe protein encoded by SEQ ID NO:94 (herein denoted SEQ ID NO:165) wasto GenBank™ accession number gi|1814196, a C. elegans ankyrin-relatedprotein, AO13. Nucleotide 1 through nucleotide 150 of SEQ ID NO:94encodes a protein that showed about 86% identity to gi|1814196. Thehighest scoring match for the protein encoded by SEQ ID NO:96 (hereindenoted SEQ ID NO:166) was to GenBank™ accession number gi|1814196, a C.elegans ankyrin-related protein, AO13. Nucleotide 3 through nucleotide161 of SEQ ID NO:96 encodes a protein that showed about 73% identity togi|1814196. The highest scoring match for the protein encoded by SEQ IDNO:98 (herein denoted SEQ ID NO:167) was to GenBank™ accession numbergi|1814196, a C. elegans ankyrin-related protein, AO13. Nucleotide 2through nucleotide 133 of SEQ ID NO:98 encodes a protein that showedabout 88% identity to gi|1814196. The highest scoring match for theprotein encoded by SEQ ID NO:100 (herein denoted SEQ ID NO:168) was toGenBank™ accession number gnl|PID|e2792, an O. volvulus E1 protein.Nucleotide 6 through nucleotide 179 of SEQ ID NO:100 encodes a proteinthat showed about 74% identity to gnl|PID|e2792. The highest scoringmatch for the protein encoded by SEQ ID NO:102 (herein denoted SEQ IDNO:169) was to GenBank™ accession number gnl|PID|e2792, an O. volvulusE1 protein. Nucleotide 1 through nucleotide 75 of SEQ ID NO:102 encodesa protein that showed about 64% identity to gi|1814196. In addition,nucleotide 136 through nucleotide 183 of SEQ ID NO:102 encodes a proteinthat showed about 93% identity to gi|1814196. The highest scoring matchfor the protein encoded by SEQ ID NO:104 (herein denoted SEQ ID NO:170)was to GenBank™ accession number gnl|PID|e2792, an O. volvulus E1protein. Nucleotide 3 through nucleotide 110 of SEQ ID NO:104 encodes aprotein that showed about 74% identity to gnl|PID|e2792. The highestscoring match for the protein encoded by SEQ ID NO:106 (herein denotedSEQ ID NO:171) was to GenBank™ accession number gnl|PID|e2792, an O.volvulus E1 protein. Nucleotide 3 through nucleotide 56 of SEQ ID NO:106encodes a protein that showed about 94% identity to gnl|PID|e2792.

Seventeen introns were identified as described above, 15 of which havenow been fully sequenced and analyzed. By comparing the D. immitisankyrin cDNA sequence with the genomic sequence, the locations of theseseventeen introns have been identified. The fifteen introns that havebeen fully sequenced, and their locations relative to SEQ ID NO:32 arelisted in Table 4.

                  TABLE 4                                                         ______________________________________                                        SEQ ID     Name/Location relative                                               NO: to SEQ ID NO:32 Designation                                             ______________________________________                                        108        Intron 152-153   DiAnk-int.sub.92                                    110 Intron 353-354 DiAnk-int.sub.118                                          112 Intron 847-848 DiAnk-int.sub.248                                          114 Intron 1034-1035 DiAnk-int.sub.94                                         116 Intron 1068-1069 DiAnk-int.sub.48                                         118 Intron 1463-1464 DiAnk-int.sub.200                                        120 Intron 1613-1614 DiAnk-int.sub.82                                         122 Intron 1784-1785 DiAnk-int.sub.213                                        124 Intron 2211-2212 DiAnk-int.sub.76                                         126 Intron 2372-2373 DiAnk-int.sub.231                                        128 Intron 2957-2958 DiAnk-int.sub.78                                         130 Intron 4494-4495 DiAnk-int.sub.110                                        132 Intron 4673-4674 DiAnk-int.sub.89                                         134 Intron 4857-4858 DiAnk-int.sub.95                                         136 Intron 5015-5016 DiAnk-int.sub.301                                      ______________________________________                                    

Table 4 lists the introns and their corresponding SEQ ID NO:s. Theintron name indicates the location of each intron relative to the D.immitis cDNA sequence, SEQ ID NO:32 (i.e., the nucleotides in the cDNAsequence between which the intron exists in the genomic DNA sequence).The intron designation includes as a subscript the size, in nucleotides,of the intron. The reverse complements of the nucleic acid sequencesdenoted SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124,SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ IDNO:134, and SEQ ID NO:136, are herein denoted SEQ ID NO:109, SEQ IDNO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129,SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, and SEQ ID NO:137,respectively.

    __________________________________________________________________________    #             SEQUENCE LISTING                                                   - -  - - (1) GENERAL INFORMATION:                                             - -    (iii) NUMBER OF SEQUENCES:  171                                        - -  - - (2) INFORMATION FOR SEQ ID NO:1:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  937 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..936                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #1:                          - - CAT CAG TTT TTG GAA TTT TCT GGA AAT CTT CT - #T CCA ATA ACC                 - #  42                                                                   His Gln Phe Leu Glu Phe Ser Gly Asn Leu Le - #u Pro Ile Thr                   1               5   - #               10                                       - - AAG AGT GGT GAC CAA CTT TCT CTT TAT TTT CT - #A CCA TTC CAA                 - #  84                                                                    Lys Ser Gly Asp Gln Leu Ser Leu Tyr Phe Le - #u Pro Phe Gln                   15                  - #20                  - #25                               - - GAA AAT CGT CTT GCT TTC ATG GTA AAG ATA CG - #C ACT CAC ACG                 - # 126                                                                    Glu Asn Arg Leu Ala Phe Met Val Lys Ile Ar - #g Thr His Thr                       30              - #    35              - #    40                           - - GAC AAC GAA ACT GCA GCT GAT GGC CGG ATA GT - #A TTT ATG AAA                 - # 168                                                                    Asp Asn Glu Thr Ala Ala Asp Gly Arg Ile Va - #l Phe Met Lys                           45          - #        50          - #        55                       - - GAA CCA AAA TTG AGA GCC GAA AAT TTA CCT CC - #G CAG ACG CCA                 - # 210                                                                    Glu Pro Lys Leu Arg Ala Glu Asn Leu Pro Pr - #o Gln Thr Pro                               60      - #            65      - #            70                   - - GTG TGT ACT CTT GCA ATC ACT CTT CCG GAA TA - #C ACT GGG CCG                 - # 252                                                                    Val Cys Thr Leu Ala Ile Thr Leu Pro Glu Ty - #r Thr Gly Pro                                   75  - #                80                                      - - GAG CCG ATG GTT TCC AAA AAA CTC TTC TAT TC - #G GAA GCT TCT                 - # 294                                                                    Glu Pro Met Val Ser Lys Lys Leu Phe Tyr Se - #r Glu Ala Ser                   85                  - #90                  - #95                               - - TTG ACT GAG AAA TAC GTT GGA GCT TTC CAT GA - #A ACT GCT GAA                 - # 336                                                                    Leu Thr Glu Lys Tyr Val Gly Ala Phe His Gl - #u Thr Ala Glu                       100              - #   105              - #   110                          - - CCT GAT AAC TTG CCA CTA GCA CAT GTT GCA CT - #A TTA ATT GGC                 - # 378                                                                    Pro Asp Asn Leu Pro Leu Ala His Val Ala Le - #u Leu Ile Gly                           115          - #       120          - #       125                      - - GCT GAT TGG CAT CGG TTA GCT CGA GCG CTT GA - #A GTA CCT GAT                 - # 420                                                                    Ala Asp Trp His Arg Leu Ala Arg Ala Leu Gl - #u Val Pro Asp                               130      - #           135      - #           140                  - - ATT GAT ATA CGA CAA GTT CGA CAT CAA CTA GT - #T GGT CTT GAA                 - # 462                                                                    Ile Asp Ile Arg Gln Val Arg His Gln Leu Va - #l Gly Leu Glu                                   145  - #               150                                     - - GCA GTC ACT ATT CTA CGT ATT TGG ATA TTT TT - #G AAG AAA GAA                 - # 504                                                                    Ala Val Thr Ile Leu Arg Ile Trp Ile Phe Le - #u Lys Lys Glu                   155                 1 - #60                 1 - #65                            - - CAA GCT ACG CCC GTT GCT TTG CGA TCA GCA TT - #G CAG CGA ATA                 - # 546                                                                    Gln Ala Thr Pro Val Ala Leu Arg Ser Ala Le - #u Gln Arg Ile                       170              - #   175              - #   180                          - - GGA CGT GAT GAT GTT GTA CGA GAA ATG GAT CG - #A GCT GAA AAG                 - # 588                                                                    Gly Arg Asp Asp Val Val Arg Glu Met Asp Ar - #g Ala Glu Lys                           185          - #       190          - #       195                      - - CTA GAT GGT TTA GAA GGA ACA CCT GTA TCG CA - #T ATT TCT GGA                 - # 630                                                                    Leu Asp Gly Leu Glu Gly Thr Pro Val Ser Hi - #s Ile Ser Gly                               200      - #           205      - #           210                  - - CCC TCA ATA ACT CTG TCA TCT ACT TTG CTA GA - #G GTA GCA GGC                 - # 672                                                                    Pro Ser Ile Thr Leu Ser Ser Thr Leu Leu Gl - #u Val Ala Gly                                   215  - #               220                                     - - GAC AGA CGT CGT CAC GCC GAG GTA ACA ATG GC - #G CAA CAG CGA                 - # 714                                                                    Asp Arg Arg Arg His Ala Glu Val Thr Met Al - #a Gln Gln Arg                   225                 2 - #30                 2 - #35                            - - TTG GCA CAA GAA CCG TTT TTT CAG CAA GTA GG - #G TAT AAT GGG                 - # 756                                                                    Leu Ala Gln Glu Pro Phe Phe Gln Gln Val Gl - #y Tyr Asn Gly                       240              - #   245              - #   250                          - - ACA CCT GGA GAT CCA GAA GAA CCC AAA GAA CA - #G TCA TTC CAC                 - # 798                                                                    Thr Pro Gly Asp Pro Glu Glu Pro Lys Glu Gl - #n Ser Phe His                           255          - #       260          - #       265                      - - GAA GAG GAA GAG GAA GTT GCA GTT TCA GAA AT - #T CGA ACA GTT                 - # 840                                                                    Glu Glu Glu Glu Glu Val Ala Val Ser Glu Il - #e Arg Thr Val                               270      - #           275      - #           280                  - - GTG CGC ACT GAA CGA CAT GTG CAT GAT TCG GA - #A AAT GGT CCT                 - # 882                                                                    Val Arg Thr Glu Arg His Val His Asp Ser Gl - #u Asn Gly Pro                                   285  - #               290                                     - - ATT GTG GAA GAG CGT ACA ATA ACA ACT ACG TA - #T GAG GAT GAT                 - # 924                                                                    Ile Val Glu Glu Arg Thr Ile Thr Thr Thr Ty - #r Glu Asp Asp                   295                 3 - #00                 3 - #05                            - - GTT GCT GTA AAC G           - #                  - #                      - #     937                                                                  Val Ala Val Asn                                                                   310                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:2:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  312 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #2:                          - - His Gln Phe Leu Glu Phe Ser Gly Asn Leu Le - #u Pro Ile Thr              1               5   - #               10                                       - - Lys Ser Gly Asp Gln Leu Ser Leu Tyr Phe Le - #u Pro Phe Gln              15                  - #20                  - #25                               - - Glu Asn Arg Leu Ala Phe Met Val Lys Ile Ar - #g Thr His Thr                  30              - #    35              - #    40                           - - Asp Asn Glu Thr Ala Ala Asp Gly Arg Ile Va - #l Phe Met Lys                      45          - #        50          - #        55                       - - Glu Pro Lys Leu Arg Ala Glu Asn Leu Pro Pr - #o Gln Thr Pro                          60      - #            65      - #            70                   - - Val Cys Thr Leu Ala Ile Thr Leu Pro Glu Ty - #r Thr Gly Pro                              75  - #                80                                      - - Glu Pro Met Val Ser Lys Lys Leu Phe Tyr Se - #r Glu Ala Ser              85                  - #90                  - #95                               - - Leu Thr Glu Lys Tyr Val Gly Ala Phe His Gl - #u Thr Ala Glu                  100              - #   105              - #   110                          - - Pro Asp Asn Leu Pro Leu Ala His Val Ala Le - #u Leu Ile Gly                      115          - #       120          - #       125                      - - Ala Asp Trp His Arg Leu Ala Arg Ala Leu Gl - #u Val Pro Asp                          130      - #           135      - #           140                  - - Ile Asp Ile Arg Gln Val Arg His Gln Leu Va - #l Gly Leu Glu                              145  - #               150                                     - - Ala Val Thr Ile Leu Arg Ile Trp Ile Phe Le - #u Lys Lys Glu              155                 1 - #60                 1 - #65                            - - Gln Ala Thr Pro Val Ala Leu Arg Ser Ala Le - #u Gln Arg Ile                  170              - #   175              - #   180                          - - Gly Arg Asp Asp Val Val Arg Glu Met Asp Ar - #g Ala Glu Lys                      185          - #       190          - #       195                      - - Leu Asp Gly Leu Glu Gly Thr Pro Val Ser Hi - #s Ile Ser Gly                          200      - #           205      - #           210                  - - Pro Ser Ile Thr Leu Ser Ser Thr Leu Leu Gl - #u Val Ala Gly                              215  - #               220                                     - - Asp Arg Arg Arg His Ala Glu Val Thr Met Al - #a Gln Gln Arg              225                 2 - #30                 2 - #35                            - - Leu Ala Gln Glu Pro Phe Phe Gln Gln Val Gl - #y Tyr Asn Gly                  240              - #   245              - #   250                          - - Thr Pro Gly Asp Pro Glu Glu Pro Lys Glu Gl - #n Ser Phe His                      255          - #       260          - #       265                      - - Glu Glu Glu Glu Glu Val Ala Val Ser Glu Il - #e Arg Thr Val                          270      - #           275      - #           280                  - - Val Arg Thr Glu Arg His Val His Asp Ser Gl - #u Asn Gly Pro                              285  - #               290                                     - - Ile Val Glu Glu Arg Thr Ile Thr Thr Thr Ty - #r Glu Asp Asp              295                 3 - #00                 3 - #05                            - - Val Ala Val Asn                                                              310                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:3:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  937 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #3:                          - - CGTTTACAGC AACATCATCC TCATACGTAG TTGTTATTGT ACGCTCTTCC  - #                  50                                                                         - - ACAATAGGAC CATTTTCCGA ATCATGCACA TGTCGTTCAG TGCGCACAAC  - #                 100                                                                         - - TGTTCGAATT TCTGAAACTG CAACTTCCTC TTCCTCTTCG TGGAATGACT  - #                 150                                                                         - - GTTCTTTGGG TTCTTCTGGA TCTCCAGGTG TCCCATTATA CCCTACTTGC  - #                 200                                                                         - - TGAAAAAACG GTTCTTGTGC CAATCGCTGT TGCGCCATTG TTACCTCGGC  - #                 250                                                                         - - GTGACGACGT CTGTCGCCTG CTACCTCTAG CAAAGTAGAT GACAGAGTTA  - #                 300                                                                         - - TTGAGGGTCC AGAAATATGC GATACAGGTG TTCCTTCTAA ACCATCTAGC  - #                 350                                                                         - - TTTTCAGCTC GATCCATTTC TCGTACAACA TCATCACGTC CTATTCGCTG  - #                 400                                                                         - - CAATGCTGAT CGCAAAGCAA CGGGCGTAGC TTGTTCTTTC TTCAAAAATA  - #                 450                                                                         - - TCCAAATACG TAGAATAGTG ACTGCTTCAA GACCAACTAG TTGATGTCGA  - #                 500                                                                         - - ACTTGTCGTA TATCAATATC AGGTACTTCA AGCGCTCGAG CTAACCGATG  - #                 550                                                                         - - CCAATCAGCG CCAATTAATA GTGCAACATG TGCTAGTGGC AAGTTATCAG  - #                 600                                                                         - - GTTCAGCAGT TTCATGGAAA GCTCCAACGT ATTTCTCAGT CAAAGAAGCT  - #                 650                                                                         - - TCCGAATAGA AGAGTTTTTT GGAAACCATC GGCTCCGGCC CAGTGTATTC  - #                 700                                                                         - - CGGAAGAGTG ATTGCAAGAG TACACACTGG CGTCTGCGGA GGTAAATTTT  - #                 750                                                                         - - CGGCTCTCAA TTTTGGTTCT TTCATAAATA CTATCCGGCC ATCAGCTGCA  - #                 800                                                                         - - GTTTCGTTGT CCGTGTGAGT GCGTATCTTT ACCATGAAAG CAAGACGATT  - #                 850                                                                         - - TTCTTGGAAT GGTAGAAAAT AAAGAGAAAG TTGGTCACCA CTCTTGGTTA  - #                 900                                                                         - - TTGGAAGAAG ATTTCCAGAA AATTCCAAAA ACTGATG      - #                       - #     937                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:4:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  936 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #4:                          - - CATCAGTTTT TGGAATTTTC TGGAAATCTT CTTCCAATAA CCAAGAGTGG  - #                  50                                                                        - - TGACCAACTT TCTCTTTATT TTCTACCATT CCAAGAAAAT CGTCTTGCTT  - #                 100                                                                         - - TCATGGTAAA GATACGCACT CACACGGACA ACGAAACTGC AGCTGATGGC  - #                 150                                                                         - - CGGATAGTAT TTATGAAAGA ACCAAAATTG AGAGCCGAAA ATTTACCTCC  - #                 200                                                                         - - GCAGACGCCA GTGTGTACTC TTGCAATCAC TCTTCCGGAA TACACTGGGC  - #                 250                                                                         - - CGGAGCCGAT GGTTTCCAAA AAACTCTTCT ATTCGGAAGC TTCTTTGACT  - #                 300                                                                         - - GAGAAATACG TTGGAGCTTT CCATGAAACT GCTGAACCTG ATAACTTGCC  - #                 350                                                                         - - ACTAGCACAT GTTGCACTAT TAATTGGCGC TGATTGGCAT CGGTTAGCTC  - #                 400                                                                         - - GAGCGCTTGA AGTACCTGAT ATTGATATAC GACAAGTTCG ACATCAACTA  - #                 450                                                                         - - GTTGGTCTTG AAGCAGTCAC TATTCTACGT ATTTGGATAT TTTTGAAGAA  - #                 500                                                                         - - AGAACAAGCT ACGCCCGTTG CTTTGCGATC AGCATTGCAG CGAATAGGAC  - #                 550                                                                         - - GTGATGATGT TGTACGAGAA ATGGATCGAG CTGAAAAGCT AGATGGTTTA  - #                 600                                                                         - - GAAGGAACAC CTGTATCGCA TATTTCTGGA CCCTCAATAA CTCTGTCATC  - #                 650                                                                         - - TACTTTGCTA GAGGTAGCAG GCGACAGACG TCGTCACGCC GAGGTAACAA  - #                 700                                                                         - - TGGCGCAACA GCGATTGGCA CAAGAACCGT TTTTTCAGCA AGTAGGGTAT  - #                 750                                                                         - - AATGGGACAC CTGGAGATCC AGAAGAACCC AAAGAACAGT CATTCCACGA  - #                 800                                                                         - - AGAGGAAGAG GAAGTTGCAG TTTCAGAAAT TCGAACAGTT GTGCGCACTG  - #                 850                                                                         - - AACGACATGT GCATGATTCG GAAAATGGTC CTATTGTGGA AGAGCGTACA  - #                 900                                                                         - - ATAACAACTA CGTATGAGGA TGATGTTGCT GTAAAC      - #                  -     #      936                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:5:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  936 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #5:                          - - GTTTACAGCA ACATCATCCT CATACGTAGT TGTTATTGTA CGCTCTTCCA  - #                  50                                                                         - - CAATAGGACC ATTTTCCGAA TCATGCACAT GTCGTTCAGT GCGCACAACT  - #                 100                                                                         - - GTTCGAATTT CTGAAACTGC AACTTCCTCT TCCTCTTCGT GGAATGACTG  - #                 150                                                                         - - TTCTTTGGGT TCTTCTGGAT CTCCAGGTGT CCCATTATAC CCTACTTGCT  - #                 200                                                                         - - GAAAAAACGG TTCTTGTGCC AATCGCTGTT GCGCCATTGT TACCTCGGCG  - #                 250                                                                         - - TGACGACGTC TGTCGCCTGC TACCTCTAGC AAAGTAGATG ACAGAGTTAT  - #                 300                                                                         - - TGAGGGTCCA GAAATATGCG ATACAGGTGT TCCTTCTAAA CCATCTAGCT  - #                 350                                                                         - - TTTCAGCTCG ATCCATTTCT CGTACAACAT CATCACGTCC TATTCGCTGC  - #                 400                                                                         - - AATGCTGATC GCAAAGCAAC GGGCGTAGCT TGTTCTTTCT TCAAAAATAT  - #                 450                                                                         - - CCAAATACGT AGAATAGTGA CTGCTTCAAG ACCAACTAGT TGATGTCGAA  - #                 500                                                                         - - CTTGTCGTAT ATCAATATCA GGTACTTCAA GCGCTCGAGC TAACCGATGC  - #                 550                                                                         - - CAATCAGCGC CAATTAATAG TGCAACATGT GCTAGTGGCA AGTTATCAGG  - #                 600                                                                         - - TTCAGCAGTT TCATGGAAAG CTCCAACGTA TTTCTCAGTC AAAGAAGCTT  - #                 650                                                                         - - CCGAATAGAA GAGTTTTTTG GAAACCATCG GCTCCGGCCC AGTGTATTCC  - #                 700                                                                         - - GGAAGAGTGA TTGCAAGAGT ACACACTGGC GTCTGCGGAG GTAAATTTTC  - #                 750                                                                         - - GGCTCTCAAT TTTGGTTCTT TCATAAATAC TATCCGGCCA TCAGCTGCAG  - #                 800                                                                         - - TTTCGTTGTC CGTGTGAGTG CGTATCTTTA CCATGAAAGC AAGACGATTT  - #                 850                                                                         - - TCTTGGAATG GTAGAAAATA AAGAGAAAGT TGGTCACCAC TCTTGGTTAT  - #                 900                                                                         - - TGGAAGAAGA TTTCCAGAAA ATTCCAAAAA CTGATG      - #                  -     #      936                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:6:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1029 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  2..811                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #6:                          - - G AAG AAA GAA CAA GCT ACG CCC GTT GCT TTG - #CGA TCA GCA                  - #   40                                                                     Lys Lys Glu Gln Ala Thr Pro Val Ala Leu Ar - #g Ser Ala                       1               5   - #                10                                      - - TTG CAG CGA ATA GGA CGT GAT GAT GTT GTA CG - #A GAA ATG GAT                 - #  82                                                                    Leu Gln Arg Ile Gly Arg Asp Asp Val Val Ar - #g Glu Met Asp                       15              - #    20              - #    25                           - - CGA GCT GAA AAG CTA GAT GGT TTA GAA GGA AC - #A CCT GTA TCG                 - # 124                                                                    Arg Ala Glu Lys Leu Asp Gly Leu Glu Gly Th - #r Pro Val Ser                           30          - #        35          - #        40                       - - CAT ATT TCT GGA CCC TCA ATA ACT CTG TCA TC - #T ACT TTG CTA                 - # 166                                                                    His Ile Ser Gly Pro Ser Ile Thr Leu Ser Se - #r Thr Leu Leu                               45      - #            50      - #            55                   - - GAG GTA GCA GGC GAC AGA CGT CGT CAC GCC GA - #G GTA ACA ATG                 - # 208                                                                    Glu Val Ala Gly Asp Arg Arg Arg His Ala Gl - #u Val Thr Met                                   60  - #                65                                      - - GCG CAA CAG CGA TTG GCA CAA GAA CCG TTT TT - #T CAG CAA GTA                 - # 250                                                                    Ala Gln Gln Arg Leu Ala Gln Glu Pro Phe Ph - #e Gln Gln Val                   70                  - #75                  - #80                               - - GGG TAT AAT GGG ACA CCT GGA GAT CCA GAA GA - #A CCC AAA GAA                 - # 292                                                                    Gly Tyr Asn Gly Thr Pro Gly Asp Pro Glu Gl - #u Pro Lys Glu                       85              - #    90              - #    95                           - - CAG TCA TTC CAC GAA GAG GAA GAG GAA GTT GC - #A GTT TCA GAA                 - # 334                                                                    Gln Ser Phe His Glu Glu Glu Glu Glu Val Al - #a Val Ser Glu                           100          - #       105          - #       110                      - - ATT CGA ACA GTT GTG CGC ACT GAA CGA CAT GT - #G CAT GAT TCG                 - # 376                                                                    Ile Arg Thr Val Val Arg Thr Glu Arg His Va - #l His Asp Ser                               115      - #           120      - #           125                  - - GAA AAT GGT CCT ATT GTG GAA GAG CGT ACA AT - #A ACA ACT ACG                 - # 418                                                                    Glu Asn Gly Pro Ile Val Glu Glu Arg Thr Il - #e Thr Thr Thr                                   130  - #               135                                     - - TAT GAG GAT GAT GTT GCT GTA AAC GAA GAA GA - #A ATT GTT GAC                 - # 460                                                                    Tyr Glu Asp Asp Val Ala Val Asn Glu Glu Gl - #u Ile Val Asp                   140                 1 - #45                 1 - #50                            - - AAA ATA GTG CCT CTC AAC GAA GAG GAG CAA GA - #A AAA TGG GAT                 - # 502                                                                    Lys Ile Val Pro Leu Asn Glu Glu Glu Gln Gl - #u Lys Trp Asp                       155              - #   160              - #   165                          - - CGA ATG GTT CGA GAA GTG GAA ATG AAT TTT GA - #G CAA CAA GAA                 - # 544                                                                    Arg Met Val Arg Glu Val Glu Met Asn Phe Gl - #u Gln Gln Glu                           170          - #       175          - #       180                      - - ACA TCA AAA GAA GGA ACG TTT GGT TGT CAG AC - #A ACA CAT GAG                 - # 586                                                                    Thr Ser Lys Glu Gly Thr Phe Gly Cys Gln Th - #r Thr His Glu                               185      - #           190      - #           195                  - - AAA GAA AAA GAT GAT GAT GGT GGC AGT CTG AA - #G ACG ACA ATG                 - # 628                                                                    Lys Glu Lys Asp Asp Asp Gly Gly Ser Leu Ly - #s Thr Thr Met                                   200  - #               205                                     - - AAA GAT AGT CAC GTA AGG CAG ATT TTC TTC GA - #T GGA GGT GAG                 - # 670                                                                    Lys Asp Ser His Val Arg Gln Ile Phe Phe As - #p Gly Gly Glu                   210                 2 - #15                 2 - #20                            - - ACA TCC GCT AAT GAA ACA GGA TTA AGT AGC GG - #G GAT GCA GAC                 - # 712                                                                    Thr Ser Ala Asn Glu Thr Gly Leu Ser Ser Gl - #y Asp Ala Asp                       225              - #   230              - #   235                          - - ACT ATT ATG ACT CCA ACG ACA AAG GAG GAT AA - #T CAT GTT ATA                 - # 754                                                                    Thr Ile Met Thr Pro Thr Thr Lys Glu Asp As - #n His Val Ile                           240          - #       245          - #       250                      - - GAC GTA ATG GAG GAA AGG CGA ACT GAT GAA GA - #G GCC AAA GGG                 - # 796                                                                    Asp Val Met Glu Glu Arg Arg Thr Asp Glu Gl - #u Ala Lys Gly                               255      - #           260      - #           265                  - - CAA AGC GTT CAT GAA TAA TCTGGATCCA CAAATTGATT TA - #AATCGCAA                 844                                                                       Gln Ser Val His Glu                                                                           270                                                            - - TCTCGCACAT GCCTATGTTG CTAATATTTA ATGAAATTTT TCAAAGCAAT  - #                 894                                                                         - - AATTTGAATG CTGTTTGGGC TTCCCATATT GTTAAAGCGT TTTCCATCGT  - #                 944                                                                         - - CCATTCACTT TTTGTTTTTG CTGTAGTCTG TAACTGCTAC TCTTGATAAA  - #                 994                                                                         - - TTTGCTCCAG TAAAAAAAAA AAAAAAAAAA AAAAA       - #                  -     #     1029                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:7:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  270 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #7:                          - - Lys Lys Glu Gln Ala Thr Pro Val Ala Leu Ar - #g Ser Ala Leu              1               5   - #               10                                       - - Gln Arg Ile Gly Arg Asp Asp Val Val Arg Gl - #u Met Asp Arg              15                  - #20                  - #25                               - - Ala Glu Lys Leu Asp Gly Leu Glu Gly Thr Pr - #o Val Ser His                  30              - #    35              - #    40                           - - Ile Ser Gly Pro Ser Ile Thr Leu Ser Ser Th - #r Leu Leu Glu                      45          - #        50          - #        55                       - - Val Ala Gly Asp Arg Arg Arg His Ala Glu Va - #l Thr Met Ala                          60      - #            65      - #            70                   - - Gln Gln Arg Leu Ala Gln Glu Pro Phe Phe Gl - #n Gln Val Gly                              75  - #                80                                      - - Tyr Asn Gly Thr Pro Gly Asp Pro Glu Glu Pr - #o Lys Glu Gln              85                  - #90                  - #95                               - - Ser Phe His Glu Glu Glu Glu Glu Val Ala Va - #l Ser Glu Ile                  100              - #   105              - #   110                          - - Arg Thr Val Val Arg Thr Glu Arg His Val Hi - #s Asp Ser Glu                      115          - #       120          - #       125                      - - Asn Gly Pro Ile Val Glu Glu Arg Thr Ile Th - #r Thr Thr Tyr                          130      - #           135      - #           140                  - - Glu Asp Asp Val Ala Val Asn Glu Glu Glu Il - #e Val Asp Lys                              145  - #               150                                     - - Ile Val Pro Leu Asn Glu Glu Glu Gln Glu Ly - #s Trp Asp Arg              155                 1 - #50                 1 - #65                            - - Met Val Arg Glu Val Glu Met Asn Phe Glu Gl - #n Gln Glu Thr                  170              - #   175              - #   180                          - - Ser Lys Glu Gly Thr Phe Gly Cys Gln Thr Th - #r His Glu Lys                      185          - #       190          - #       195                      - - Glu Lys Asp Asp Asp Gly Gly Ser Leu Lys Th - #r Thr Met Lys                          200      - #           205      - #           210                  - - Asp Ser His Val Arg Gln Ile Phe Phe Asp Gl - #y Gly Glu Thr                              215  - #               220                                     - - Ser Ala Asn Glu Thr Gly Leu Ser Ser Gly As - #p Ala Asp Thr              225                 2 - #30                 2 - #35                            - - Ile Met Thr Pro Thr Thr Lys Glu Asp Asn Hi - #s Val Ile Asp                  240              - #   245              - #   250                          - - Val Met Glu Glu Arg Arg Thr Asp Glu Glu Al - #a Lys Gly Gln                      255          - #       260          - #       265                      - - Ser Val His Glu                                                                      270                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:8:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1029 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #8:                          - - TTTTTTTTTT TTTTTTTTTT TTTTACTGGA GCAAATTTAT CAAGAGTAGC  - #                  50                                                                         - - AGTTACAGAC TACAGCAAAA ACAAAAAGTG AATGGACGAT GGAAAACGCT  - #                 100                                                                         - - TTAACAATAT GGGAAGCCCA AACAGCATTC AAATTATTGC TTTGAAAAAT  - #                 150                                                                         - - TTCATTAAAT ATTAGCAACA TAGGCATGTG CGAGATTGCG ATTTAAATCA  - #                 200                                                                         - - ATTTGTGGAT CCAGATTATT CATGAACGCT TTGCCCTTTG GCCTCTTCAT  - #                 250                                                                         - - CAGTTCGCCT TTCCTCCATT ACGTCTATAA CATGATTATC CTCCTTTGTC  - #                 300                                                                         - - GTTGGAGTCA TAATAGTGTC TGCATCCCCG CTACTTAATC CTGTTTCATT  - #                 350                                                                         - - AGCGGATGTC TCACCTCCAT CGAAGAAAAT CTGCCTTACG TGACTATCTT  - #                 400                                                                         - - TCATTGTCGT CTTCAGACTG CCACCATCAT CATCTTTTTC TTTCTCATGT  - #                 450                                                                         - - GTTGTCTGAC AACCAAACGT TCCTTCTTTT GATGTTTCTT GTTGCTCAAA  - #                 500                                                                         - - ATTCATTTCC ACTTCTCGAA CCATTCGATC CCATTTTTCT TGCTCCTCTT  - #                 550                                                                         - - CGTTGAGAGG CACTATTTTG TCAACAATTT CTTCTTCGTT TACAGCAACA  - #                 600                                                                         - - TCATCCTCAT ACGTAGTTGT TATTGTACGC TCTTCCACAA TAGGACCATT  - #                 650                                                                         - - TTCCGAATCA TGCACATGTC GTTCAGTGCG CACAACTGTT CGAATTTCTG  - #                 700                                                                         - - AAACTGCAAC TTCCTCTTCC TCTTCGTGGA ATGACTGTTC TTTGGGTTCT  - #                 750                                                                         - - TCTGGATCTC CAGGTGTCCC ATTATACCCT ACTTGCTGAA AAAACGGTTC  - #                 800                                                                         - - TTGTGCCAAT CGCTGTTGCG CCATTGTTAC CTCGGCGTGA CGACGTCTGT  - #                 850                                                                         - - CGCCTGCTAC CTCTAGCAAA GTAGATGACA GAGTTATTGA GGGTCCAGAA  - #                 900                                                                         - - ATATGCGATA CAGGTGTTCC TTCTAAACCA TCTAGCTTTT CAGCTCGATC  - #                 950                                                                         - - CATTTCTCGT ACAACATCAT CACGTCCTAT TCGCTGCAAT GCTGATCGCA  - #                1000                                                                         - - AAGCAACGGG CGTAGCTTGT TCTTTCTTC         - #                  - #              1029                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:9:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  810 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #9:                          - - AAGAAAGAAC AAGCTACGCC CGTTGCTTTG CGATCAGCAT TGCAGCGAAT  - #                  50                                                                         - - AGGACGTGAT GATGTTGTAC GAGAAATGGA TCGAGCTGAA AAGCTAGATG  - #                 100                                                                         - - GTTTAGAAGG AACACCTGTA TCGCATATTT CTGGACCCTC AATAACTCTG  - #                 150                                                                         - - TCATCTACTT TGCTAGAGGT AGCAGGCGAC AGACGTCGTC ACGCCGAGGT  - #                 200                                                                         - - AACAATGGCG CAACAGCGAT TGGCACAAGA ACCGTTTTTT CAGCAAGTAG  - #                 250                                                                         - - GGTATAATGG GACACCTGGA GATCCAGAAG AACCCAAAGA ACAGTCATTC  - #                 300                                                                         - - CACGAAGAGG AAGAGGAAGT TGCAGTTTCA GAAATTCGAA CAGTTGTGCG  - #                 350                                                                         - - CACTGAACGA CATGTGCATG ATTCGGAAAA TGGTCCTATT GTGGAAGAGC  - #                 400                                                                         - - GTACAATAAC AACTACGTAT GAGGATGATG TTGCTGTAAA CGAAGAAGAA  - #                 450                                                                         - - ATTGTTGACA AAATAGTGCC TCTCAACGAA GAGGAGCAAG AAAAATGGGA  - #                 500                                                                         - - TCGAATGGTT CGAGAAGTGG AAATGAATTT TGAGCAACAA GAAACATCAA  - #                 550                                                                         - - AAGAAGGAAC GTTTGGTTGT CAGACAACAC ATGAGAAAGA AAAAGATGAT  - #                 600                                                                         - - GATGGTGGCA GTCTGAAGAC GACAATGAAA GATAGTCACG TAAGGCAGAT  - #                 650                                                                         - - TTTCTTCGAT GGAGGTGAGA CATCCGCTAA TGAAACAGGA TTAAGTAGCG  - #                 700                                                                         - - GGGATGCAGA CACTATTATG ACTCCAACGA CAAAGGAGGA TAATCATGTT  - #                 750                                                                         - - ATAGACGTAA TGGAGGAAAG GCGAACTGAT GAAGAGGCCA AAGGGCAAAG  - #                 800                                                                         - - CGTTCATGAA                - #                  - #                      - #       810                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:10:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  810 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #10:                         - - TTCATGAACG CTTTGCCCTT TGGCCTCTTC ATCAGTTCGC CTTTCCTCCA  - #                  50                                                                         - - TTACGTCTAT AACATGATTA TCCTCCTTTG TCGTTGGAGT CATAATAGTG  - #                 100                                                                         - - TCTGCATCCC CGCTACTTAA TCCTGTTTCA TTAGCGGATG TCTCACCTCC  - #                 150                                                                         - - ATCGAAGAAA ATCTGCCTTA CGTGACTATC TTTCATTGTC GTCTTCAGAC  - #                 200                                                                         - - TGCCACCATC ATCATCTTTT TCTTTCTCAT GTGTTGTCTG ACAACCAAAC  - #                 250                                                                         - - GTTCCTTCTT TTGATGTTTC TTGTTGCTCA AAATTCATTT CCACTTCTCG  - #                 300                                                                         - - AACCATTCGA TCCCATTTTT CTTGCTCCTC TTCGTTGAGA GGCACTATTT  - #                 350                                                                         - - TGTCAACAAT TTCTTCTTCG TTTACAGCAA CATCATCCTC ATACGTAGTT  - #                 400                                                                         - - GTTATTGTAC GCTCTTCCAC AATAGGACCA TTTTCCGAAT CATGCACATG  - #                 450                                                                         - - TCGTTCAGTG CGCACAACTG TTCGAATTTC TGAAACTGCA ACTTCCTCTT  - #                 500                                                                         - - CCTCTTCGTG GAATGACTGT TCTTTGGGTT CTTCTGGATC TCCAGGTGTC  - #                 550                                                                         - - CCATTATACC CTACTTGCTG AAAAAACGGT TCTTGTGCCA ATCGCTGTTG  - #                 600                                                                         - - CGCCATTGTT ACCTCGGCGT GACGACGTCT GTCGCCTGCT ACCTCTAGCA  - #                 650                                                                         - - AAGTAGATGA CAGAGTTATT GAGGGTCCAG AAATATGCGA TACAGGTGTT  - #                 700                                                                         - - CCTTCTAAAC CATCTAGCTT TTCAGCTCGA TCCATTTCTC GTACAACATC  - #                 750                                                                         - - ATCACGTCCT ATTCGCTGCA ATGCTGATCG CAAAGCAACG GGCGTAGCTT  - #                 800                                                                         - - GTTCTTTCTT                - #                  - #                      - #       810                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:11:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  600 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..600                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #11:                         - - GCC CAG CCA GTT CCA CAA GAG ATA GTC ACT CG - #T TTA CAT GGG                 - #  42                                                                    Ala Gln Pro Val Pro Gln Glu Ile Val Thr Ar - #g Leu His Gly                   1               5   - #                10                                      - - AAT AGA GTC GCT GTT TCT CCA ATT GTA ACT GT - #T GAA CCG CGT                 - #  84                                                                    Asn Arg Val Ala Val Ser Pro Ile Val Thr Va - #l Glu Pro Arg                   15                  - #20                  - #25                               - - CGT CGC AAA TTC CAT AAG CCC ATA ACG CTG TG - #C ATA CCA TTG                 - # 126                                                                    Arg Arg Lys Phe His Lys Pro Ile Thr Leu Cy - #s Ile Pro Leu                       30              - #    35              - #    40                           - - CCA CAA AGC TCA AAT AAA GGA ATG TTA ACA CA - #A TAT AGT GGC                 - # 168                                                                    Pro Gln Ser Ser Asn Lys Gly Met Leu Thr Gl - #n Tyr Ser Gly                           45          - #        50          - #        55                       - - CAA CCA GGA CAG GAA CCA CCG ACG CTG CGT TT - #A CTC TGC AGT                 - # 210                                                                    Gln Pro Gly Gln Glu Pro Pro Thr Leu Arg Le - #u Leu Cys Ser                               60      - #            65      - #            70                   - - AAA ACT GGA GGT TCT TCT CCT GCA CAG TGG GA - #A GAT ATT ACT                 - # 252                                                                    Lys Thr Gly Gly Ser Ser Pro Ala Gln Trp Gl - #u Asp Ile Thr                                   75  - #                80                                      - - GGA ACT ACC CAG TTA ACA TTT ACT GGT GAG GA - #C GTT TCA TTT                 - # 294                                                                    Gly Thr Thr Gln Leu Thr Phe Thr Gly Glu As - #p Val Ser Phe                   85                  - #90                  - #95                               - - ACA ACT ACG GTT TCT GCT CGA TTT TGG TTG AT - #G GAT TGC CAA                 - # 336                                                                    Thr Thr Thr Val Ser Ala Arg Phe Trp Leu Me - #t Asp Cys Gln                       100              - #   105              - #   110                          - - ACT CCG CGA GAT GCG GCA CGA ATG GCA CAA GA - #A GTT TAC AAT                 - # 378                                                                    Thr Pro Arg Asp Ala Ala Arg Met Ala Gln Gl - #u Val Tyr Asn                           115          - #       120          - #       125                      - - GAA GCA ATT GCA GTT CCT TAT ATG GCT AAA TT - #T CTT ATT TTT                 - # 420                                                                    Glu Ala Ile Ala Val Pro Tyr Met Ala Lys Ph - #e Leu Ile Phe                               130      - #           135      - #           140                  - - GCT CGA CGA ACT TTT CCT GCC GAA GGA CAG TT - #G AGA TTG TTT                 - # 462                                                                    Ala Arg Arg Thr Phe Pro Ala Glu Gly Gln Le - #u Arg Leu Phe                                   145  - #               150                                     - - TGT ATG ACT GAT GAT CGG GAA GAT AAA ACC CT - #G GAA AAA CAA                 - # 504                                                                    Cys Met Thr Asp Asp Arg Glu Asp Lys Thr Le - #u Glu Lys Gln                   155                 1 - #60                 1 - #65                            - - GAA CGT TTC ATT GAA ATT GCG AAA TCG AAA GA - #T GTA GAA GTC                 - # 546                                                                    Glu Arg Phe Ile Glu Ile Ala Lys Ser Lys As - #p Val Glu Val                       170              - #   175              - #   180                          - - TTA AGT GGG CGA CAT CAG TTT TTG GAA TTT TC - #T GGA AAT CTT                 - # 588                                                                    Leu Ser Gly Arg His Gln Phe Leu Glu Phe Se - #r Gly Asn Leu                           185          - #       190          - #       195                      - - CTT CCA ATA ACC            - #                  - #                      - #      600                                                                  Leu Pro Ile Thr                                                                           200                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:12:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  200 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #12:                         - - Ala Gln Pro Val Pro Gln Glu Ile Val Thr Ar - #g Leu His Gly               1               5  - #                10                                      - - Asn Arg Val Ala Val Ser Pro Ile Val Thr Va - #l Glu Pro Arg              15                  - #20                  - #25                               - - Arg Arg Lys Phe His Lys Pro Ile Thr Leu Cy - #s Ile Pro Leu                  30              - #    35              - #    40                           - - Pro Gln Ser Ser Asn Lys Gly Met Leu Thr Gl - #n Tyr Ser Gly                      45          - #        50          - #        55                       - - Gln Pro Gly Gln Glu Pro Pro Thr Leu Arg Le - #u Leu Cys Ser                          60      - #            65      - #            70                   - - Lys Thr Gly Gly Ser Ser Pro Ala Gln Trp Gl - #u Asp Ile Thr                              75  - #                80                                      - - Gly Thr Thr Gln Leu Thr Phe Thr Gly Glu As - #p Val Ser Phe              85                  - #90                  - #95                               - - Thr Thr Thr Val Ser Ala Arg Phe Trp Leu Me - #t Asp Cys Gln                  100              - #   105              - #   110                          - - Thr Pro Arg Asp Ala Ala Arg Met Ala Gln Gl - #u Val Tyr Asn                      115          - #       120          - #       125                      - - Glu Ala Ile Ala Val Pro Tyr Met Ala Lys Ph - #e Leu Ile Phe                          130      - #           135      - #           140                  - - Ala Arg Arg Thr Phe Pro Ala Glu Gly Gln Le - #u Arg Leu Phe                              145  - #               150                                     - - Cys Met Thr Asp Asp Arg Glu Asp Lys Thr Le - #u Glu Lys Gln              155                 1 - #60                 1 - #65                            - - Glu Arg Phe Ile Glu Ile Ala Lys Ser Lys As - #p Val Glu Val                  170              - #   175              - #   180                          - - Leu Ser Gly Arg His Gln Phe Leu Glu Phe Se - #r Gly Asn Leu                      185          - #       190          - #       195                      - - Leu Pro Ile Thr                                                                      200                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:13:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  600 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #13:                         - - GGTTATTGGA AGAAGATTTC CAGAAAATTC CAAAAACTGA TGTCGCCCAC  - #                  50                                                                         - - TTAAGACTTC TACATCTTTC GATTTCGCAA TTTCAATGAA ACGTTCTTGT  - #                 100                                                                         - - TTTTCCAGGG TTTTATCTTC CCGATCATCA GTCATACAAA ACAATCTCAA  - #                 150                                                                         - - CTGTCCTTCG GCAGGAAAAG TTCGTCGAGC AAAAATAAGA AATTTAGCCA  - #                 200                                                                         - - TATAAGGAAC TGCAATTGCT TCATTGTAAA CTTCTTGTGC CATTCGTGCC  - #                 250                                                                         - - GCATCTCGCG GAGTTTGGCA ATCCATCAAC CAAAATCGAG CAGAAACCGT  - #                 300                                                                         - - AGTTGTAAAT GAAACGTCCT CACCAGTAAA TGTTAACTGG GTAGTTCCAG  - #                 350                                                                         - - TAATATCTTC CCACTGTGCA GGAGAAGAAC CTCCAGTTTT ACTGCAGAGT  - #                 400                                                                         - - AAACGCAGCG TCGGTGGTTC CTGTCCTGGT TGGCCACTAT ATTGTGTTAA  - #                 450                                                                         - - CATTCCTTTA TTTGAGCTTT GTGGCAATGG TATGCACAGC GTTATGGGCT  - #                 500                                                                         - - TATGGAATTT GCGACGACGC GGTTCAACAG TTACAATTGG AGAAACAGCG  - #                 550                                                                         - - ACTCTATTCC CATGTAAACG AGTGACTATC TCTTGTGGAA CTGGCTGGGC  - #                 600                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:14:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1228 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..1227                                               - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #14:                         - - CAT CAA GCT GCT CAG CAA GGG CAT AAC AGT GT - #T GTA CGT TAC                 - #  42                                                                    His Gln Ala Ala Gln Gln Gly His Asn Ser Va - #l Val Arg Tyr                   1               5   - #               10                                       - - TTG TTG GAA CAT GGT GCA AGT CCA AAT GTT CA - #T ACA TCG ACA                 - #  84                                                                    Leu Leu Glu His Gly Ala Ser Pro Asn Val Hi - #s Thr Ser Thr                   15                  - #20                  - #25                               - - GGA CAA ACT CCA TTA TCG ATT GCT GAA CGT CT - #A GGG TAT GTA                 - # 126                                                                    Gly Gln Thr Pro Leu Ser Ile Ala Glu Arg Le - #u Gly Tyr Val                   30                  - #35                  - #40                               - - TCC GTG GTT GAA GCG CTT AAA ACA ATT ACC GA - #G ACT ACT GTG                 - # 168                                                                    Ser Val Val Glu Ala Leu Lys Thr Ile Thr Gl - #u Thr Thr Val                   45                  - #50                  - #55                               - - ATA ACG GAG ACC ACA ACC GTT ACT GAA GAA AG - #A TAT AAA CCT                 - # 210                                                                    Ile Thr Glu Thr Thr Thr Val Thr Glu Glu Ar - #g Tyr Lys Pro                   60                  - #65                  - #70                               - - CAG AAT CCC GAA GCA ATG AAT GAA ACC ATG TT - #T TCC GAT TCC                 - # 252                                                                    Gln Asn Pro Glu Ala Met Asn Glu Thr Met Ph - #e Ser Asp Ser                   75                  - #80                                                      - - GAA GAT GAA GGT GAA GAT AAT CAG ATC ACA GC - #C AAT GCT CAT                 - # 294                                                                    Glu Asp Glu Gly Glu Asp Asn Gln Ile Thr Al - #a Asn Ala His                   85                  - #90                  - #95                               - - GCT CAT GAT TTC TCA GAA AGC CTC ACA AAA GG - #T TTG CAC GAT                 - # 336                                                                    Ala His Asp Phe Ser Glu Ser Leu Thr Lys Gl - #y Leu His Asp                   100                 1 - #05                 1 - #10                            - - TCA ACT GGT GTA CAT TTG ATT CAT GCC ACA GA - #A CCG ACA TTG                 - # 378                                                                    Ser Thr Gly Val His Leu Ile His Ala Thr Gl - #u Pro Thr Leu                   115                 1 - #20                 1 - #25                            - - TCA CGA AGT CCG GAA GTG GAA GGT ACG GAT GG - #C GAT TTG GAT                 - # 420                                                                    Ser Arg Ser Pro Glu Val Glu Gly Thr Asp Gl - #y Asp Leu Asp                   130                 1 - #35                 1 - #40                            - - GCC TTA ATT CGT AAA GCA CAA CAT GAA CCA AT - #T ACT ACA GCG                 - # 462                                                                    Ala Leu Ile Arg Lys Ala Gln His Glu Pro Il - #e Thr Thr Ala                   145                 1 - #50                                                    - - ATG GCC GAT CCT TCC TTA GAT GCA TCG CTT CC - #T GAC AAT GTT                 - # 504                                                                    Met Ala Asp Pro Ser Leu Asp Ala Ser Leu Pr - #o Asp Asn Val                   155                 1 - #60                 1 - #65                            - - ACG ATA ATG AGA ACT ACC ATG CAA CCT AGT TT - #T TTA ATT TCG                 - # 546                                                                    Thr Ile Met Arg Thr Thr Met Gln Pro Ser Ph - #e Leu Ile Ser                   170                 1 - #75                 1 - #80                            - - TTT ATG GTG GAT GCA CGT GGA GGA GCA ATG CG - #T GGT TGT AGG                 - # 588                                                                    Phe Met Val Asp Ala Arg Gly Gly Ala Met Ar - #g Gly Cys Arg                   185                 1 - #90                 1 - #95                            - - CAT TCC GGT GTC AGA ATC ATT ATA CCA CCG AG - #G AAA GCG CCG                 - # 630                                                                    His Ser Gly Val Arg Ile Ile Ile Pro Pro Ar - #g Lys Ala Pro                   200                 2 - #05                 2 - #10                            - - CAA CCT ACA CGG GTC ACA TGC AGA TAC CTT GG - #A AAG GAC AAG                 - # 672                                                                    Gln Pro Thr Arg Val Thr Cys Arg Tyr Leu Gl - #y Lys Asp Lys                   215                 2 - #20                                                    - - TTA GCG CAT CCA CCA CCA TTA AGT GAA GGT GA - #A GCG CTC GCN                 - # 714                                                                    Leu Ala His Pro Pro Pro Leu Ser Glu Gly Gl - #u Ala Leu Ala                   225                 2 - #30                 2 - #35                            - - TCA CGT ATA CTT GAA ATG GCA CCA CAT GGA GC - #A AAA TTC TTA                 - # 756                                                                    Ser Arg Ile Leu Glu Met Ala Pro His Gly Al - #a Lys Phe Leu                   240                 2 - #45                 2 - #50                            - - GGC CCT GTT ATA TTG GAA GTA CCA CAT TTT GC - #A TCA CTT CGT                 - # 798                                                                    Gly Pro Val Ile Leu Glu Val Pro His Phe Al - #a Ser Leu Arg                   255                 2 - #60                 2 - #65                            - - GGA CGA GAG AGA GAG ATT GTC ATT TTG CGT TC - #T GAT GAT GGG                 - # 840                                                                    Gly Arg Glu Arg Glu Ile Val Ile Leu Arg Se - #r Asp Asp Gly                   270                 2 - #75                 2 - #80                            - - CAG CAT TGG AAA GAG CAT CAG CTT GAA GCA AC - #A GAA GAT GCT                 - # 882                                                                    Gln His Trp Lys Glu His Gln Leu Glu Ala Th - #r Glu Asp Ala                   285                 2 - #90                                                    - - GTA CAA GAG GTG CTC AAT GAA TCG TTT GAT GC - #A GAA GAG TTG                 - # 924                                                                    Val Gln Glu Val Leu Asn Glu Ser Phe Asp Al - #a Glu Glu Leu                   295                 3 - #00                 3 - #05                            - - TCG CAA CTT GAT GAT TTG CAT ACA TCA CGG AT - #T ACG CGT ATC                 - # 966                                                                    Ser Gln Leu Asp Asp Leu His Thr Ser Arg Il - #e Thr Arg Ile                   310                 3 - #15                 3 - #20                            - - CTG ACC AAT GAT TTC CCA ATG TAT TTC GCG GT - #C GTT ACT CGT                 - #1008                                                                    Leu Thr Asn Asp Phe Pro Met Tyr Phe Ala Va - #l Val Thr Arg                   325                 3 - #30                 3 - #35                            - - GTG CGG CAA GAA GTG CAC TGT GTT GGT CCA GA - #A GGT GGT GTA                 - #1050                                                                    Val Arg Gln Glu Val His Cys Val Gly Pro Gl - #u Gly Gly Val                   340                 3 - #45                 3 - #50                            - - ATA CTC TCT TCA GTT GTT CCT CAT GTG CAG GC - #C ATA TTT CCG                 - #1092                                                                    Ile Leu Ser Ser Val Val Pro His Val Gln Al - #a Ile Phe Pro                   355                 3 - #60                                                    - - GAT GGT TCC TTG ACT AAG ACG ATC AAA GTA TC - #T GTG CAA GCC                 - #1134                                                                    Asp Gly Ser Leu Thr Lys Thr Ile Lys Val Se - #r Val Gln Ala                   365                 3 - #70                 3 - #75                            - - CAG CCA GTT CCA CAA GAG ATA GTC ACT CGT TT - #A CAT GGG AAT                 - #1176                                                                    Gln Pro Val Pro Gln Glu Ile Val Thr Arg Le - #u His Gly Asn                   380                 3 - #85                 3 - #90                            - - AGA GTC GCT GTT TCT CCA ATT GTA ACT GTT GA - #A CCG CGT CGT                 - #1218                                                                    Arg Val Ala Val Ser Pro Ile Val Thr Val Gl - #u Pro Arg Arg                   395                 4 - #00                 4 - #05                            - - CGC AAA TTC C             - #                  - #                      - #      1228                                                                  Arg Lys Phe                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:15:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  409 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #15:                         - - His Gln Ala Ala Gln Gln Gly His Asn Ser Va - #l Val Arg Tyr               1               5  - #                10                                      - - Leu Leu Glu His Gly Ala Ser Pro Asn Val Hi - #s Thr Ser Thr              15                  - #20                  - #25                               - - Gly Gln Thr Pro Leu Ser Ile Ala Glu Arg Le - #u Gly Tyr Val                  30              - #    35              - #    40                           - - Ser Val Val Glu Ala Leu Lys Thr Ile Thr Gl - #u Thr Thr Val                      45          - #        50          - #        55                       - - Ile Thr Glu Thr Thr Thr Val Thr Glu Glu Ar - #g Tyr Lys Pro                          60      - #            65      - #            70                   - - Gln Asn Pro Glu Ala Met Asn Glu Thr Met Ph - #e Ser Asp Ser                              75  - #                80                                      - - Glu Asp Glu Gly Glu Asp Asn Gln Ile Thr Al - #a Asn Ala His              85                  - #90                  - #95                               - - Ala His Asp Phe Ser Glu Ser Leu Thr Lys Gl - #y Leu His Asp                  100              - #   105              - #   110                          - - Ser Thr Gly Val His Leu Ile His Ala Thr Gl - #u Pro Thr Leu                      115          - #       120          - #       125                      - - Ser Arg Ser Pro Glu Val Glu Gly Thr Asp Gl - #y Asp Leu Asp                          130      - #           135      - #           140                  - - Ala Leu Ile Arg Lys Ala Gln His Glu Pro Il - #e Thr Thr Ala                              145  - #               150                                     - - Met Ala Asp Pro Ser Leu Asp Ala Ser Leu Pr - #o Asp Asn Val              155                 1 - #60                 1 - #65                            - - Thr Ile Met Arg Thr Thr Met Gln Pro Ser Ph - #e Leu Ile Ser                  170              - #   175              - #   180                          - - Phe Met Val Asp Ala Arg Gly Gly Ala Met Ar - #g Gly Cys Arg                      185          - #       190          - #       195                      - - His Ser Gly Val Arg Ile Ile Ile Pro Pro Ar - #g Lys Ala Pro                          200      - #           205      - #           210                  - - Gln Pro Thr Arg Val Thr Cys Arg Tyr Leu Gl - #y Lys Asp Lys                              215  - #               220                                     - - Leu Ala His Pro Pro Pro Leu Ser Glu Gly Gl - #u Ala Leu Ala              225                 2 - #30                 2 - #35                            - - Ser Arg Ile Leu Glu Met Ala Pro His Gly Al - #a Lys Phe Leu                  240              - #   245              - #   250                          - - Gly Pro Val Ile Leu Glu Val Pro His Phe Al - #a Ser Leu Arg                      255          - #       260          - #       265                      - - Gly Arg Glu Arg Glu Ile Val Ile Leu Arg Se - #r Asp Asp Gly                          270      - #           275      - #           280                  - - Gln His Trp Lys Glu His Gln Leu Glu Ala Th - #r Glu Asp Ala                              285  - #               290                                     - - Val Gln Glu Val Leu Asn Glu Ser Phe Asp Al - #a Glu Glu Leu              295                 3 - #00                 3 - #05                            - - Ser Gln Leu Asp Asp Leu His Thr Ser Arg Il - #e Thr Arg Ile                  310              - #   315              - #   320                          - - Leu Thr Asn Asp Phe Pro Met Tyr Phe Ala Va - #l Val Thr Arg                      325          - #       330          - #       335                      - - Val Arg Gln Glu Val His Cys Val Gly Pro Gl - #u Gly Gly Val                          340      - #           345      - #           350                  - - Ile Leu Ser Ser Val Val Pro His Val Gln Al - #a Ile Phe Pro                              355  - #               360                                     - - Asp Gly Ser Leu Thr Lys Thr Ile Lys Val Se - #r Val Gln Ala              365                 3 - #70                 3 - #75                            - - Gln Pro Val Pro Gln Glu Ile Val Thr Arg Le - #u His Gly Asn                  380              - #   385              - #   390                          - - Arg Val Ala Val Ser Pro Ile Val Thr Val Gl - #u Pro Arg Arg                      395          - #       400          - #       405                      - - Arg Lys Phe                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:16:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1228 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #16:                         - - GGAATTTGCG ACGACGCGGT TCAACAGTTA CAATTGGAGA AACAGCGACT  - #                  50                                                                         - - CTATTCCCAT GTAAACGAGT GACTATCTCT TGTGGAACTG GCTGGGCTTG  - #                 100                                                                         - - CACAGATACT TTGATCGTCT TAGTCAAGGA ACCATCCGGA AATATGGCCT  - #                 150                                                                         - - GCACATGAGG AACAACTGAA GAGAGTATTA CACCACCTTC TGGACCAACA  - #                 200                                                                         - - CAGTGCACTT CTTGCCGCAC ACGAGTAACG ACCGCGAAAT ACATTGGGAA  - #                 250                                                                         - - ATCATTGGTC AGGATACGCG TAATCCGTGA TGTATGCAAA TCATCAAGTT  - #                 300                                                                         - - GCGACAACTC TTCTGCATCA AACGATTCAT TGAGCACCTC TTGTACAGCA  - #                 350                                                                         - - TCTTCTGTTG CTTCAAGCTG ATGCTCTTTC CAATGCTGCC CATCATCAGA  - #                 400                                                                         - - ACGCAAAATG ACAATCTCTC TCTCTCGTCC ACGAAGTGAT GCAAAATGTG  - #                 450                                                                         - - GTACTTCCAA TATAACAGGG CCTAAGAATT TTGCTCCATG TGGTGCCATT  - #                 500                                                                         - - TCAAGTATAC GTGANGCGAG CGCTTCACCT TCACTTAATG GTGGTGGATG  - #                 550                                                                         - - CGCTAACTTG TCCTTTCCAA GGTATCTGCA TGTGACCCGT GTAGGTTGCG  - #                 600                                                                         - - GCGCTTTCCT CGGTGGTATA ATGATTCTGA CACCGGAATG CCTACAACCA  - #                 650                                                                         - - CGCATTGCTC CTCCACGTGC ATCCACCATA AACGAAATTA AAAAACTAGG  - #                 700                                                                         - - TTGCATGGTA GTTCTCATTA TCGTAACATT GTCAGGAAGC GATGCATCTA  - #                 750                                                                         - - AGGAAGGATC GGCCATCGCT GTAGTAATTG GTTCATGTTG TGCTTTACGA  - #                 800                                                                         - - ATTAAGGCAT CCAAATCGCC ATCCGTACCT TCCACTTCCG GACTTCGTGA  - #                 850                                                                         - - CAATGTCGGT TCTGTGGCAT GAATCAAATG TACACCAGTT GAATCGTGCA  - #                 900                                                                         - - AACCTTTTGT GAGGCTTTCT GAGAAATCAT GAGCATGAGC ATTGGCTGTG  - #                 950                                                                         - - ATCTGATTAT CTTCACCTTC ATCTTCGGAA TCGGAAAACA TGGTTTCATT  - #                1000                                                                         - - CATTGCTTCG GGATTCTGAG GTTTATATCT TTCTTCAGTA ACGGTTGTGG  - #                1050                                                                         - - TCTCCGTTAT CACAGTAGTC TCGGTAATTG TTTTAAGCGC TTCAACCACG  - #                1100                                                                         - - GATACATACC CTAGACGTTC AGCAATCGAT AATGGAGTTT GTCCTGTCGA  - #                1150                                                                         - - TGTATGAACA TTTGGACTTG CACCATGTTC CAACAAGTAA CGTACAACAC  - #                1200                                                                         - - TGTTATGCCC TTGCTGAGCA GCTTGATG         - #                  - #               1228                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:17:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1227 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #17:                         - - CATCAAGCTG CTCAGCAAGG GCATAACAGT GTTGTACGTT ACTTGTTGGA  - #                  50                                                                         - - ACATGGTGCA AGTCCAAATG TTCATACATC GACAGGACAA ACTCCATTAT  - #                 100                                                                         - - CGATTGCTGA ACGTCTAGGG TATGTATCCG TGGTTGAAGC GCTTAAAACA  - #                 150                                                                         - - ATTACCGAGA CTACTGTGAT AACGGAGACC ACAACCGTTA CTGAAGAAAG  - #                 200                                                                         - - ATATAAACCT CAGAATCCCG AAGCAATGAA TGAAACCATG TTTTCCGATT  - #                 250                                                                         - - CCGAAGATGA AGGTGAAGAT AATCAGATCA CAGCCAATGC TCATGCTCAT  - #                 300                                                                         - - GATTTCTCAG AAAGCCTCAC AAAAGGTTTG CACGATTCAA CTGGTGTACA  - #                 350                                                                         - - TTTGATTCAT GCCACAGAAC CGACATTGTC ACGAAGTCCG GAAGTGGAAG  - #                 400                                                                         - - GTACGGATGG CGATTTGGAT GCCTTAATTC GTAAAGCACA ACATGAACCA  - #                 450                                                                         - - ATTACTACAG CGATGGCCGA TCCTTCCTTA GATGCATCGC TTCCTGACAA  - #                 500                                                                         - - TGTTACGATA ATGAGAACTA CCATGCAACC TAGTTTTTTA ATTTCGTTTA  - #                 550                                                                         - - TGGTGGATGC ACGTGGAGGA GCAATGCGTG GTTGTAGGCA TTCCGGTGTC  - #                 600                                                                         - - AGAATCATTA TACCACCGAG GAAAGCGCCG CAACCTACAC GGGTCACATG  - #                 650                                                                         - - CAGATACCTT GGAAAGGACA AGTTAGCGCA TCCACCACCA TTAAGTGAAG  - #                 700                                                                         - - GTGAAGCGCT CGCNTCACGT ATACTTGAAA TGGCACCACA TGGAGCAAAA  - #                 750                                                                         - - TTCTTAGGCC CTGTTATATT GGAAGTACCA CATTTTGCAT CACTTCGTGG  - #                 800                                                                         - - ACGAGAGAGA GAGATTGTCA TTTTGCGTTC TGATGATGGG CAGCATTGGA  - #                 850                                                                         - - AAGAGCATCA GCTTGAAGCA ACAGAAGATG CTGTACAAGA GGTGCTCAAT  - #                 900                                                                         - - GAATCGTTTG ATGCAGAAGA GTTGTCGCAA CTTGATGATT TGCATACATC  - #                 950                                                                         - - ACGGATTACG CGTATCCTGA CCAATGATTT CCCAATGTAT TTCGCGGTCG  - #                1000                                                                         - - TTACTCGTGT GCGGCAAGAA GTGCACTGTG TTGGTCCAGA AGGTGGTGTA  - #                1050                                                                         - - ATACTCTCTT CAGTTGTTCC TCATGTGCAG GCCATATTTC CGGATGGTTC  - #                1100                                                                         - - CTTGACTAAG ACGATCAAAG TATCTGTGCA AGCCCAGCCA GTTCCACAAG  - #                1150                                                                         - - AGATAGTCAC TCGTTTACAT GGGAATAGAG TCGCTGTTTC TCCAATTGTA  - #                1200                                                                         - - ACTGTTGAAC CGCGTCGTCG CAAATTC          - #                  - #               1227                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:18:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1227 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #18:                         - - GAATTTGCGA CGACGCGGTT CAACAGTTAC AATTGGAGAA ACAGCGACTC  - #                  50                                                                         - - TATTCCCATG TAAACGAGTG ACTATCTCTT GTGGAACTGG CTGGGCTTGC  - #                 100                                                                         - - ACAGATACTT TGATCGTCTT AGTCAAGGAA CCATCCGGAA ATATGGCCTG  - #                 150                                                                         - - CACATGAGGA ACAACTGAAG AGAGTATTAC ACCACCTTCT GGACCAACAC  - #                 200                                                                         - - AGTGCACTTC TTGCCGCACA CGAGTAACGA CCGCGAAATA CATTGGGAAA  - #                 250                                                                         - - TCATTGGTCA GGATACGCGT AATCCGTGAT GTATGCAAAT CATCAAGTTG  - #                 300                                                                         - - CGACAACTCT TCTGCATCAA ACGATTCATT GAGCACCTCT TGTACAGCAT  - #                 350                                                                         - - CTTCTGTTGC TTCAAGCTGA TGCTCTTTCC AATGCTGCCC ATCATCAGAA  - #                 400                                                                         - - CGCAAAATGA CAATCTCTCT CTCTCGTCCA CGAAGTGATG CAAAATGTGG  - #                 450                                                                         - - TACTTCCAAT ATAACAGGGC CTAAGAATTT TGCTCCATGT GGTGCCATTT  - #                 500                                                                         - - CAAGTATACG TGANGCGAGC GCTTCACCTT CACTTAATGG TGGTGGATGC  - #                 550                                                                         - - GCTAACTTGT CCTTTCCAAG GTATCTGCAT GTGACCCGTG TAGGTTGCGG  - #                 600                                                                         - - CGCTTTCCTC GGTGGTATAA TGATTCTGAC ACCGGAATGC CTACAACCAC  - #                 650                                                                         - - GCATTGCTCC TCCACGTGCA TCCACCATAA ACGAAATTAA AAAACTAGGT  - #                 700                                                                         - - TGCATGGTAG TTCTCATTAT CGTAACATTG TCAGGAAGCG ATGCATCTAA  - #                 750                                                                         - - GGAAGGATCG GCCATCGCTG TAGTAATTGG TTCATGTTGT GCTTTACGAA  - #                 800                                                                         - - TTAAGGCATC CAAATCGCCA TCCGTACCTT CCACTTCCGG ACTTCGTGAC  - #                 850                                                                         - - AATGTCGGTT CTGTGGCATG AATCAAATGT ACACCAGTTG AATCGTGCAA  - #                 900                                                                         - - ACCTTTTGTG AGGCTTTCTG AGAAATCATG AGCATGAGCA TTGGCTGTGA  - #                 950                                                                         - - TCTGATTATC TTCACCTTCA TCTTCGGAAT CGGAAAACAT GGTTTCATTC  - #                1000                                                                         - - ATTGCTTCGG GATTCTGAGG TTTATATCTT TCTTCAGTAA CGGTTGTGGT  - #                1050                                                                         - - CTCCGTTATC ACAGTAGTCT CGGTAATTGT TTTAAGCGCT TCAACCACGG  - #                1100                                                                         - - ATACATACCC TAGACGTTCA GCAATCGATA ATGGAGTTTG TCCTGTCGAT  - #                1150                                                                         - - GTATGAACAT TTGGACTTGC ACCATGTTCC AACAAGTAAC GTACAACACT  - #                1200                                                                         - - GTTATGCCCT TGCTGAGCAG CTTGATG          - #                  - #               1227                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:19:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  573 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..573                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #19:                         - - AAT AAC GAC AAG GTA GCA TTG TTA CTT CTA GA - #A AAT GGT GCT                 - #  42                                                                    Asn Asn Asp Lys Val Ala Leu Leu Leu Leu Gl - #u Asn Gly Ala                   1               5   - #               10                                       - - TCT GCA CAT GCC GCT GCC AAG AAT GGG TAC AC - #T CCT TTA CAT                 - #  84                                                                    Ser Ala His Ala Ala Ala Lys Asn Gly Tyr Th - #r Pro Leu His                   15                  - #20                  - #25                               - - ATT GCC GCG AAG AAG AAT CAG ATG GAT ATT GC - #T AGC ACT CTC                 - # 126                                                                    Ile Ala Ala Lys Lys Asn Gln Met Asp Ile Al - #a Ser Thr Leu                   30                  - #35                  - #40                               - - CTT CAT TAT AAG GCA AAT GCG AAT GCT GAA AG - #C AAA GCT GGC                 - # 168                                                                    Leu His Tyr Lys Ala Asn Ala Asn Ala Glu Se - #r Lys Ala Gly                   45                  - #50                  - #55                               - - TTT ACA CCA CTT CAT CTT GCC GCC CAG GAG GG - #C CAT CGC GAA                 - # 210                                                                    Phe Thr Pro Leu His Leu Ala Ala Gln Glu Gl - #y His Arg Glu                   60                  - #65                  - #70                               - - ATG GCT GCG TTA TTA ATT GAA AAT GGA GCA AA - #A GTT GGA GCT                 - # 252                                                                    Met Ala Ala Leu Leu Ile Glu Asn Gly Ala Ly - #s Val Gly Ala                   75                  - #80                                                      - - CAG GCA AGG AAT GGC TTG ACA CCA ATG CAT TT - #A TGT GCA CAG                 - # 294                                                                    Gln Ala Arg Asn Gly Leu Thr Pro Met His Le - #u Cys Ala Gln                   85                  - #90                  - #95                               - - GAG GAT CGT GTG AGC GTA GCA GAA GAA CTA GT - #G AAA GAA AAC                 - # 336                                                                    Glu Asp Arg Val Ser Val Ala Glu Glu Leu Va - #l Lys Glu Asn                   100                 1 - #05                 1 - #10                            - - GCA GCC ATT GAT CCC AAA ACG AAA GCA GGA TA - #T ACG CCG TTA                 - # 378                                                                    Ala Ala Ile Asp Pro Lys Thr Lys Ala Gly Ty - #r Thr Pro Leu                   115                 1 - #20                 1 - #25                            - - CAT GTT GCT TGC CAT TTT GGA CAA ATA AAC AT - #G GTC CGT TTC                 - # 420                                                                    His Val Ala Cys His Phe Gly Gln Ile Asn Me - #t Val Arg Phe                   130                 1 - #35                 1 - #40                            - - TTG ATT GAG CAT GGC GCA CGA GTT TCA GTT AT - #T ACT CGT GCT                 - # 462                                                                    Leu Ile Glu His Gly Ala Arg Val Ser Val Il - #e Thr Arg Ala                   145                 1 - #50                                                    - - TCC TAT ACT CCT CTG CAT CAA GCT GCT CAG CA - #A GGG CAT AAC                 - # 504                                                                    Ser Tyr Thr Pro Leu His Gln Ala Ala Gln Gl - #n Gly His Asn                   155                 1 - #60                 1 - #65                            - - AGT GTT GTA CGT TAC TTG TTG GAA CAT GGT GC - #A AGT CCA AAT                 - # 546                                                                    Ser Val Val Arg Tyr Leu Leu Glu His Gly Al - #a Ser Pro Asn                   170                 1 - #75                 1 - #80                            - - GTT CAT ACA TCG ACA GGA CAA ACT CCA    - #                  - #                573                                                                     Val His Thr Ser Thr Gly Gln Thr Pro                                           185                 1 - #90                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:20:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  191 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #20:                         - - Asn Asn Asp Lys Val Ala Leu Leu Leu Leu Gl - #u Asn Gly Ala               1               5  - #                10                                      - - Ser Ala His Ala Ala Ala Lys Asn Gly Tyr Th - #r Pro Leu His              15                  - #20                  - #25                               - - Ile Ala Ala Lys Lys Asn Gln Met Asp Ile Al - #a Ser Thr Leu                  30              - #    35              - #    40                           - - Leu His Tyr Lys Ala Asn Ala Asn Ala Glu Se - #r Lys Ala Gly                      45          - #        50          - #        55                       - - Phe Thr Pro Leu His Leu Ala Ala Gln Glu Gl - #y His Arg Glu                          60      - #            65      - #            70                   - - Met Ala Ala Leu Leu Ile Glu Asn Gly Ala Ly - #s Val Gly Ala                              75  - #                80                                      - - Gln Ala Arg Asn Gly Leu Thr Pro Met His Le - #u Cys Ala Gln              85                  - #90                  - #95                               - - Glu Asp Arg Val Ser Val Ala Glu Glu Leu Va - #l Lys Glu Asn                  100              - #   105              - #   110                          - - Ala Ala Ile Asp Pro Lys Thr Lys Ala Gly Ty - #r Thr Pro Leu                      115          - #       120          - #       125                      - - His Val Ala Cys His Phe Gly Gln Ile Asn Me - #t Val Arg Phe                          130      - #           135      - #           140                  - - Leu Ile Glu His Gly Ala Arg Val Ser Val Il - #e Thr Arg Ala                              145  - #               150                                     - - Ser Tyr Thr Pro Leu His Gln Ala Ala Gln Gl - #n Gly His Asn              155                 1 - #60                 1 - #65                            - - Ser Val Val Arg Tyr Leu Leu Glu His Gly Al - #a Ser Pro Asn                  170              - #   175              - #   180                          - - Val His Thr Ser Thr Gly Gln Thr Pro                                              185          - #       190                                             - -  - - (2) INFORMATION FOR SEQ ID NO:21:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  573 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #21:                         - - TGGAGTTTGT CCTGTCGATG TATGAACATT TGGACTTGCA CCATGTTCCA  - #                  50                                                                         - - ACAAGTAACG TACAACACTG TTATGCCCTT GCTGAGCAGC TTGATGCAGA  - #                 100                                                                         - - GGAGTATAGG AAGCACGAGT AATAACTGAA ACTCGTGCGC CATGCTCAAT  - #                 150                                                                         - - CAAGAAACGG ACCATGTTTA TTTGTCCAAA ATGGCAAGCA ACATGTAACG  - #                 200                                                                         - - GCGTATATCC TGCTTTCGTT TTGGGATCAA TGGCTGCGTT TTCTTTCACT  - #                 250                                                                         - - AGTTCTTCTG CTACGCTCAC ACGATCCTCC TGTGCACATA AATGCATTGG  - #                 300                                                                         - - TGTCAAGCCA TTCCTTGCCT GAGCTCCAAC TTTTGCTCCA TTTTCAATTA  - #                 350                                                                         - - ATAACGCAGC CATTTCGCGA TGGCCCTCCT GGGCGGCAAG ATGAAGTGGT  - #                 400                                                                         - - GTAAAGCCAG CTTTGCTTTC AGCATTCGCA TTTGCCTTAT AATGAAGGAG  - #                 450                                                                         - - AGTGCTAGCA ATATCCATCT GATTCTTCTT CGCGGCAATA TGTAAAGGAG  - #                 500                                                                         - - TGTACCCATT CTTGGCAGCG GCATGTGCAG AAGCACCATT TTCTAGAAGT  - #                 550                                                                         - - AACAATGCTA CCTTGTCGTT ATT           - #                  - #                   573                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:22:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  911 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..909                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #22:                         - - GTG GAT GAT GTT ACT GTT GAC TAT CTC ACT CC - #T CTT CAT GTG                 - #  42                                                                    Val Asp Asp Val Thr Val Asp Tyr Leu Thr Pr - #o Leu His Val                   1               5   - #               10                                       - - GCT GCT CAT TGC GGA CAT GTC CGT GTC GCT AA - #A CTT TTG CTG                 - #  84                                                                    Ala Ala His Cys Gly His Val Arg Val Ala Ly - #s Leu Leu Leu                   15                  - #20                  - #25                               - - GAT CGT AAT GCT GAC CCG AAT GCT CGA GCT CT - #C AAT GGC TTC                 - # 126                                                                    Asp Arg Asn Ala Asp Pro Asn Ala Arg Ala Le - #u Asn Gly Phe                   30                  - #35                  - #40                               - - ACA CCG CTG CAT ATC GCT TGC AAA AAA AAT CG - #C ATT AAA ATT                 - # 168                                                                    Thr Pro Leu His Ile Ala Cys Lys Lys Asn Ar - #g Ile Lys Ile                   45                  - #50                  - #55                               - - GTC GAA CTG CTA CTG AAA TAC CAC GCT GCA AT - #C GAA GCA ACT                 - # 210                                                                    Val Glu Leu Leu Leu Lys Tyr His Ala Ala Il - #e Glu Ala Thr                   60                  - #65                  - #70                               - - ACT GAA TCC GGT CTC TCA CCG CTG CAT GTC GC - #T GCT TTT ATG                 - # 252                                                                    Thr Glu Ser Gly Leu Ser Pro Leu His Val Al - #a Ala Phe Met                   75                  - #80                                                      - - GGT GCT ATA AAC ATT GTC ATC TAT TTA CTA CA - #A CAA GGT GCT                 - # 294                                                                    Gly Ala Ile Asn Ile Val Ile Tyr Leu Leu Gl - #n Gln Gly Ala                   85                  - #90                  - #95                               - - AAT GCA GAT GTG GCT ACA GTA CGC GGT GAA AC - #G CCT CTT CAT                 - # 336                                                                    Asn Ala Asp Val Ala Thr Val Arg Gly Glu Th - #r Pro Leu His                   100                 1 - #05                 1 - #10                            - - TTA GCT GCA CGA GCA AAC CAA ACG GAC ATT GT - #T CGT GTT TTG                 - # 378                                                                    Leu Ala Ala Arg Ala Asn Gln Thr Asp Ile Va - #l Arg Val Leu                   115                 1 - #20                 1 - #25                            - - GTG CGT AAT GGA GCA CAG GTG GAT GCT GCT GC - #T CGT GAA CTA                 - # 420                                                                    Val Arg Asn Gly Ala Gln Val Asp Ala Ala Al - #a Arg Glu Leu                   130                 1 - #35                 1 - #40                            - - CAA ACT CCA CTG CAC ATT GCA TCA CGT CTT GG - #T AAT ACC GAC                 - # 462                                                                    Gln Thr Pro Leu His Ile Ala Ser Arg Leu Gl - #y Asn Thr Asp                   145                 1 - #50                                                    - - ATC GTC ATT TTG TTG CTG CAG GCT AAT GCA TC - #A CCA AAT GCT                 - # 504                                                                    Ile Val Ile Leu Leu Leu Gln Ala Asn Ala Se - #r Pro Asn Ala                   155                 1 - #60                 1 - #65                            - - GCC ACA AGA GAT CTT TAT ACT CCT CTT CAT AT - #T GCT GCC AAG                 - # 546                                                                    Ala Thr Arg Asp Leu Tyr Thr Pro Leu His Il - #e Ala Ala Lys                   170                 1 - #75                 1 - #80                            - - GAG GGG CAA GAG GAA GTG GCA GCA ATA TTG AT - #G GAT CAT GGA                 - # 588                                                                    Glu Gly Gln Glu Glu Val Ala Ala Ile Leu Me - #t Asp His Gly                   185                 1 - #90                 1 - #95                            - - ACC GAC AAG ACA CTG CTC ACG AAA AAG GGT TT - #T ACG CCG TTG                 - # 630                                                                    Thr Asp Lys Thr Leu Leu Thr Lys Lys Gly Ph - #e Thr Pro Leu                   200                 2 - #05                 2 - #10                            - - CAT TTA GCT GCT AAG TAT GGC AAT TTG CCG GT - #C GCG AAA TCA                 - # 672                                                                    His Leu Ala Ala Lys Tyr Gly Asn Leu Pro Va - #l Ala Lys Ser                   215                 2 - #20                                                    - - TTG CTA GAA CGA GGA ACA CCG GTT GAC ATT GA - #A GGC AAG AAT                 - # 714                                                                    Leu Leu Glu Arg Gly Thr Pro Val Asp Ile Gl - #u Gly Lys Asn                   225                 2 - #30                 2 - #35                            - - CAG GTA ACA CCT CTG CAT GTA GCG GCA CAT TA - #C AAT AAC GAC                 - # 756                                                                    Gln Val Thr Pro Leu His Val Ala Ala His Ty - #r Asn Asn Asp                   240                 2 - #45                 2 - #50                            - - AAG GTA GCA TTG TTA CTT CTA GAA AAT GGT GC - #T TCT GCA CAT                 - # 798                                                                    Lys Val Ala Leu Leu Leu Leu Glu Asn Gly Al - #a Ser Ala His                   255                 2 - #60                 2 - #65                            - - GCC GCT GCC AAG AAT GGG TAC ACT CCT TTA CA - #T ATT GCC GCG                 - # 840                                                                    Ala Ala Ala Lys Asn Gly Tyr Thr Pro Leu Hi - #s Ile Ala Ala                   270                 2 - #75                 2 - #80                            - - AAG AAG AAT CAG ATG GAT ATT GCT AGC ACT CT - #C CTT CAT TAT                 - # 882                                                                    Lys Lys Asn Gln Met Asp Ile Ala Ser Thr Le - #u Leu His Tyr                   285                 2 - #90                                                    - - AAG GCA AAT GCG AAT GCT GAA AGC AAA GC  - #                  - #               911                                                                     Lys Ala Asn Ala Asn Ala Glu Ser Lys                                           295                 3 - #00                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:23:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  303 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #23:                         - - Val Asp Asp Val Thr Val Asp Tyr Leu Thr Pr - #o Leu His Val               1               5  - #                10                                      - - Ala Ala His Cys Gly His Val Arg Val Ala Ly - #s Leu Leu Leu              15                  - #20                  - #25                               - - Asp Arg Asn Ala Asp Pro Asn Ala Arg Ala Le - #u Asn Gly Phe                  30              - #    35              - #    40                           - - Thr Pro Leu His Ile Ala Cys Lys Lys Asn Ar - #g Ile Lys Ile                      45          - #        50          - #        55                       - - Val Glu Leu Leu Leu Lys Tyr His Ala Ala Il - #e Glu Ala Thr                          60      - #            65      - #            70                   - - Thr Glu Ser Gly Leu Ser Pro Leu His Val Al - #a Ala Phe Met                              75  - #                80                                      - - Gly Ala Ile Asn Ile Val Ile Tyr Leu Leu Gl - #n Gln Gly Ala              85                  - #90                  - #95                               - - Asn Ala Asp Val Ala Thr Val Arg Gly Glu Th - #r Pro Leu His                  100              - #   105              - #   110                          - - Leu Ala Ala Arg Ala Asn Gln Thr Asp Ile Va - #l Arg Val Leu                      115          - #       120          - #       125                      - - Val Arg Asn Gly Ala Gln Val Asp Ala Ala Al - #a Arg Glu Leu                          130      - #           135      - #           140                  - - Gln Thr Pro Leu His Ile Ala Ser Arg Leu Gl - #y Asn Thr Asp                              145  - #               150                                     - - Ile Val Ile Leu Leu Leu Gln Ala Asn Ala Se - #r Pro Asn Ala              155                 1 - #60                 1 - #65                            - - Ala Thr Arg Asp Leu Tyr Thr Pro Leu His Il - #e Ala Ala Lys                  170              - #   175              - #   180                          - - Glu Gly Gln Glu Glu Val Ala Ala Ile Leu Me - #t Asp His Gly                      185          - #       190          - #       195                      - - Thr Asp Lys Thr Leu Leu Thr Lys Lys Gly Ph - #e Thr Pro Leu                          200      - #           205      - #           210                  - - His Leu Ala Ala Lys Tyr Gly Asn Leu Pro Va - #l Ala Lys Ser                              215  - #               220                                     - - Leu Leu Glu Arg Gly Thr Pro Val Asp Ile Gl - #u Gly Lys Asn              225                 2 - #30                 2 - #35                            - - Gln Val Thr Pro Leu His Val Ala Ala His Ty - #r Asn Asn Asp                  240              - #   245              - #   250                          - - Lys Val Ala Leu Leu Leu Leu Glu Asn Gly Al - #a Ser Ala His                      255          - #       260          - #       265                      - - Ala Ala Ala Lys Asn Gly Tyr Thr Pro Leu Hi - #s Ile Ala Ala                          270      - #           275      - #           280                  - - Lys Lys Asn Gln Met Asp Ile Ala Ser Thr Le - #u Leu His Tyr                              285  - #               290                                     - - Lys Ala Asn Ala Asn Ala Glu Ser Lys                                      295                 3 - #00                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:24:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  911 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #24:                         - - GCTTTGCTTT CAGCATTCGC ATTTGCCTTA TAATGAAGGA GAGTGCTAGC  - #                  50                                                                         - - AATATCCATC TGATTCTTCT TCGCGGCAAT ATGTAAAGGA GTGTACCCAT  - #                 100                                                                         - - TCTTGGCAGC GGCATGTGCA GAAGCACCAT TTTCTAGAAG TAACAATGCT  - #                 150                                                                         - - ACCTTGTCGT TATTGTAATG TGCCGCTACA TGCAGAGGTG TTACCTGATT  - #                 200                                                                         - - CTTGCCTTCA ATGTCAACCG GTGTTCCTCG TTCTAGCAAT GATTTCGCGA  - #                 250                                                                         - - CCGGCAAATT GCCATACTTA GCAGCTAAAT GCAACGGCGT AAAACCCTTT  - #                 300                                                                         - - TTCGTGAGCA GTGTCTTGTC GGTTCCATGA TCCATCAATA TTGCTGCCAC  - #                 350                                                                         - - TTCCTCTTGC CCCTCCTTGG CAGCAATATG AAGAGGAGTA TAAAGATCTC  - #                 400                                                                         - - TTGTGGCAGC ATTTGGTGAT GCATTAGCCT GCAGCAACAA AATGACGATG  - #                 450                                                                         - - TCGGTATTAC CAAGACGTGA TGCAATGTGC AGTGGAGTTT GTAGTTCACG  - #                 500                                                                         - - AGCAGCAGCA TCCACCTGTG CTCCATTACG CACCAAAACA CGAACAATGT  - #                 550                                                                         - - CCGTTTGGTT TGCTCGTGCA GCTAAATGAA GAGGCGTTTC ACCGCGTACT  - #                 600                                                                         - - GTAGCCACAT CTGCATTAGC ACCTTGTTGT AGTAAATAGA TGACAATGTT  - #                 650                                                                         - - TATAGCACCC ATAAAAGCAG CGACATGCAG CGGTGAGAGA CCGGATTCAG  - #                 700                                                                         - - TAGTTGCTTC GATTGCAGCG TGGTATTTCA GTAGCAGTTC GACAATTTTA  - #                 750                                                                         - - ATGCGATTTT TTTTGCAAGC GATATGCAGC GGTGTGAAGC CATTGAGAGC  - #                 800                                                                         - - TCGAGCATTC GGGTCAGCAT TACGATCCAG CAAAAGTTTA GCGACACGGA  - #                 850                                                                         - - CATGTCCGCA ATGAGCAGCC ACATGAAGAG GAGTGAGATA GTCAACAGTA  - #                 900                                                                         - - ACATCATCCA C               - #                  - #                      - #      911                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:25:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  909 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #25:                         - - GTGGATGATG TTACTGTTGA CTATCTCACT CCTCTTCATG TGGCTGCTCA  - #                  50                                                                         - - TTGCGGACAT GTCCGTGTCG CTAAACTTTT GCTGGATCGT AATGCTGACC  - #                 100                                                                         - - CGAATGCTCG AGCTCTCAAT GGCTTCACAC CGCTGCATAT CGCTTGCAAA  - #                 150                                                                         - - AAAAATCGCA TTAAAATTGT CGAACTGCTA CTGAAATACC ACGCTGCAAT  - #                 200                                                                         - - CGAAGCAACT ACTGAATCCG GTCTCTCACC GCTGCATGTC GCTGCTTTTA  - #                 250                                                                         - - TGGGTGCTAT AAACATTGTC ATCTATTTAC TACAACAAGG TGCTAATGCA  - #                 300                                                                         - - GATGTGGCTA CAGTACGCGG TGAAACGCCT CTTCATTTAG CTGCACGAGC  - #                 350                                                                         - - AAACCAAACG GACATTGTTC GTGTTTTGGT GCGTAATGGA GCACAGGTGG  - #                 400                                                                         - - ATGCTGCTGC TCGTGAACTA CAAACTCCAC TGCACATTGC ATCACGTCTT  - #                 450                                                                         - - GGTAATACCG ACATCGTCAT TTTGTTGCTG CAGGCTAATG CATCACCAAA  - #                 500                                                                         - - TGCTGCCACA AGAGATCTTT ATACTCCTCT TCATATTGCT GCCAAGGAGG  - #                 550                                                                         - - GGCAAGAGGA AGTGGCAGCA ATATTGATGG ATCATGGAAC CGACAAGACA  - #                 600                                                                         - - CTGCTCACGA AAAAGGGTTT TACGCCGTTG CATTTAGCTG CTAAGTATGG  - #                 650                                                                         - - CAATTTGCCG GTCGCGAAAT CATTGCTAGA ACGAGGAACA CCGGTTGACA  - #                 700                                                                         - - TTGAAGGCAA GAATCAGGTA ACACCTCTGC ATGTAGCGGC ACATTACAAT  - #                 750                                                                         - - AACGACAAGG TAGCATTGTT ACTTCTAGAA AATGGTGCTT CTGCACATGC  - #                 800                                                                         - - CGCTGCCAAG AATGGGTACA CTCCTTTACA TATTGCCGCG AAGAAGAATC  - #                 850                                                                         - - AGATGGATAT TGCTAGCACT CTCCTTCATT ATAAGGCAAA TGCGAATGCT  - #                 900                                                                         - - GAAAGCAAA                - #                  - #                       - #        909                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:26:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  909 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #26:                         - - TTTGCTTTCA GCATTCGCAT TTGCCTTATA ATGAAGGAGA GTGCTAGCAA  - #                  50                                                                        - - TATCCATCTG ATTCTTCTTC GCGGCAATAT GTAAAGGAGT GTACCCATTC  - #                 100                                                                         - - TTGGCAGCGG CATGTGCAGA AGCACCATTT TCTAGAAGTA ACAATGCTAC  - #                 150                                                                         - - CTTGTCGTTA TTGTAATGTG CCGCTACATG CAGAGGTGTT ACCTGATTCT  - #                 200                                                                         - - TGCCTTCAAT GTCAACCGGT GTTCCTCGTT CTAGCAATGA TTTCGCGACC  - #                 250                                                                         - - GGCAAATTGC CATACTTAGC AGCTAAATGC AACGGCGTAA AACCCTTTTT  - #                 300                                                                         - - CGTGAGCAGT GTCTTGTCGG TTCCATGATC CATCAATATT GCTGCCACTT  - #                 350                                                                         - - CCTCTTGCCC CTCCTTGGCA GCAATATGAA GAGGAGTATA AAGATCTCTT  - #                 400                                                                         - - GTGGCAGCAT TTGGTGATGC ATTAGCCTGC AGCAACAAAA TGACGATGTC  - #                 450                                                                         - - GGTATTACCA AGACGTGATG CAATGTGCAG TGGAGTTTGT AGTTCACGAG  - #                 500                                                                         - - CAGCAGCATC CACCTGTGCT CCATTACGCA CCAAAACACG AACAATGTCC  - #                 550                                                                         - - GTTTGGTTTG CTCGTGCAGC TAAATGAAGA GGCGTTTCAC CGCGTACTGT  - #                 600                                                                         - - AGCCACATCT GCATTAGCAC CTTGTTGTAG TAAATAGATG ACAATGTTTA  - #                 650                                                                         - - TAGCACCCAT AAAAGCAGCG ACATGCAGCG GTGAGAGACC GGATTCAGTA  - #                 700                                                                         - - GTTGCTTCGA TTGCAGCGTG GTATTTCAGT AGCAGTTCGA CAATTTTAAT  - #                 750                                                                         - - GCGATTTTTT TTGCAAGCGA TATGCAGCGG TGTGAAGCCA TTGAGAGCTC  - #                 800                                                                         - - GAGCATTCGG GTCAGCATTA CGATCCAGCA AAAGTTTAGC GACACGGACA  - #                 850                                                                         - - TGTCCGCAAT GAGCAGCCAC ATGAAGAGGA GTGAGATAGT CAACAGTAAC  - #                 900                                                                         - - ATCATCCAC                - #                  - #                       - #        909                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:27:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1096 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  51..1094                                              - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #27:                         - - GGTTTAATTA CCCAAGTTTG AGGCGGCTGA CTGATATAAC TCAACTATTG  - #                  50                                                                        - - ATG AGT AAT CCT ATA GTC GAG GGA AGT GGC TG - #G CCC GCA GAA                 - #  92                                                                    Met Ser Asn Pro Ile Val Glu Gly Ser Gly Tr - #p Pro Ala Glu                   1               5   - #               10                                       - - CCA AAA GAT TCA CAA CAT CAA CAA CAA ATT CC - #T GAT GAT AAC                 - # 134                                                                    Pro Lys Asp Ser Gln His Gln Gln Gln Ile Pr - #o Asp Asp Asn                   15                  - #20                  - #25                               - - AGT CAA CAT TCC AAC AAA GGT GAG AGC AGT GC - #A AGT TTT TTA                 - # 176                                                                    Ser Gln His Ser Asn Lys Gly Glu Ser Ser Al - #a Ser Phe Leu                   30                  - #35                  - #40                               - - CGA GCA GCA AGA GCT GGA AAT TTG GAT CGT GT - #A CTT GAA CTA                 - # 218                                                                    Arg Ala Ala Arg Ala Gly Asn Leu Asp Arg Va - #l Leu Glu Leu                   45                  - #50                  - #55                               - - CTT CGT TCG GGC ACC GAT ATC AAC ACA TGC AA - #T GCG AAT GGC                 - # 260                                                                    Leu Arg Ser Gly Thr Asp Ile Asn Thr Cys As - #n Ala Asn Gly                   60                  - #65                  - #70                               - - CTT AAT GCA TTG CAT CTG GCC TCC AAA GAA GG - #T CAT CAT GAA                 - # 302                                                                    Leu Asn Ala Leu His Leu Ala Ser Lys Glu Gl - #y His His Glu                   75                  - #80                                                      - - GTG GTC CGC GAA CTT CTG AAA AGA AAA GCA GA - #T GTT GAT GCT                 - # 344                                                                    Val Val Arg Glu Leu Leu Lys Arg Lys Ala As - #p Val Asp Ala                   85                  - #90                  - #95                               - - GCC ACT AGA AAG GGT AAC ACA GCG TTA CAT AT - #A GCA TCA TTG                 - # 386                                                                    Ala Thr Arg Lys Gly Asn Thr Ala Leu His Il - #e Ala Ser Leu                   100                 1 - #05                 1 - #10                            - - GCA GGA CAA GAA CTA ATC GTC ACA GTA CTT GT - #T GAA AAT GGT                 - # 428                                                                    Ala Gly Gln Glu Leu Ile Val Thr Val Leu Va - #l Glu Asn Gly                   115                 1 - #20                 1 - #25                            - - GCT AAT GTT AAC GTA CAA TCA CTA AAC GGT TT - #T ACA CCA CTT                 - # 470                                                                    Ala Asn Val Asn Val Gln Ser Leu Asn Gly Ph - #e Thr Pro Leu                   130                 1 - #35                 1 - #40                            - - TAC ATG GCT GCA CAA GAA AAT CAC GAA TCT GT - #T GTA CGC TAT                 - # 512                                                                    Tyr Met Ala Ala Gln Glu Asn His Glu Ser Va - #l Val Arg Tyr                   145                 1 - #50                                                    - - CTT CTT GCC CAC AAT GCC AAT CAA GCT TTA AG - #T ACA GAA GAC                 - # 554                                                                    Leu Leu Ala His Asn Ala Asn Gln Ala Leu Se - #r Thr Glu Asp                   155                 1 - #60                 1 - #65                            - - GGT TTT ACG CCA CTG GCA GTT GCC TTG CAA CA - #A GGT CAC GAT                 - # 596                                                                    Gly Phe Thr Pro Leu Ala Val Ala Leu Gln Gl - #n Gly His Asp                   170                 1 - #75                 1 - #80                            - - CGT GTG GTC GCT GTT TTG CTT GAA AAT GAC AC - #G CGC GGG AAA                 - # 638                                                                    Arg Val Val Ala Val Leu Leu Glu Asn Asp Th - #r Arg Gly Lys                   185                 1 - #90                 1 - #95                            - - GTG CGC TTG CCA GCA CTG CAT ATT GCT GCT AA - #A AAA GAT GAT                 - # 680                                                                    Val Arg Leu Pro Ala Leu His Ile Ala Ala Ly - #s Lys Asp Asp                   200                 2 - #05                 2 - #10                            - - ACG AAA GCA GCT ACG CTA TTA CTT CAA AAT GA - #G CAT AAC TCG                 - # 722                                                                    Thr Lys Ala Ala Thr Leu Leu Leu Gln Asn Gl - #u His Asn Ser                   215                 2 - #20                                                    - - GAT GTG ACT TCG AAA AGC GGC TTT ACT CCG CT - #T CAT ATC GCC                 - # 764                                                                    Asp Val Thr Ser Lys Ser Gly Phe Thr Pro Le - #u His Ile Ala                   225                 2 - #30                 2 - #35                            - - GCT CAC TAT GGA AAT GAG AAC GTA GCA CAA CT - #G CTA CTC GAA                 - # 806                                                                    Ala His Tyr Gly Asn Glu Asn Val Ala Gln Le - #u Leu Leu Glu                   240                 2 - #45                 2 - #50                            - - AAG GGA GCC AAT GTG AAT TAC CAA GCG AGA CA - #T AAC ATA AGT                 - # 848                                                                    Lys Gly Ala Asn Val Asn Tyr Gln Ala Arg Hi - #s Asn Ile Ser                   255                 2 - #60                 2 - #65                            - - CCG TTA CAC GTT GCA ACA AAA TGG GGT CGT AC - #A AAC ATG GTT                 - # 890                                                                    Pro Leu His Val Ala Thr Lys Trp Gly Arg Th - #r Asn Met Val                   270                 2 - #75                 2 - #80                            - - TCG TTA TTG TTG GCT CAT GGG GCC GTA ATT GA - #C TGT CGC ACA                 - # 932                                                                    Ser Leu Leu Leu Ala His Gly Ala Val Ile As - #p Cys Arg Thr                   285                 2 - #90                                                    - - CGT GAT TTA CTA ACA CCA TTA CAC TGT GCT TC - #T CGT TCA GGT                 - # 974                                                                    Arg Asp Leu Leu Thr Pro Leu His Cys Ala Se - #r Arg Ser Gly                   295                 3 - #00                 3 - #05                            - - CAT GAT CAA GTT GTT GAT TTG TTG CTT GAA AA - #A GGA GCT CCA                 - #1016                                                                    His Asp Gln Val Val Asp Leu Leu Leu Glu Ly - #s Gly Ala Pro                   310                 3 - #15                 3 - #20                            - - ATC AGT GCT AAG ACA AAA AAT GGT TTG GCT CC - #C TTA CAT ATG                 - #1058                                                                    Ile Ser Ala Lys Thr Lys Asn Gly Leu Ala Pr - #o Leu His Met                   325                 3 - #30                 3 - #35                            - - GCA GCA CAG GTG GAT GAT GTT ACT GTT GAC TA - #T CTC AC                   - #   1096                                                                    Ala Ala Gln Val Asp Asp Val Thr Val Asp Ty - #r Leu                           340                 3 - #45                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:28:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  348 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #28:                         - - Met Ser Asn Pro Ile Val Glu Gly Ser Gly Tr - #p Pro Ala Glu               1               5  - #                10                                      - - Pro Lys Asp Ser Gln His Gln Gln Gln Ile Pr - #o Asp Asp Asn              15                  - #20                  - #25                               - - Ser Gln His Ser Asn Lys Gly Glu Ser Ser Al - #a Ser Phe Leu                  30              - #    35              - #    40                           - - Arg Ala Ala Arg Ala Gly Asn Leu Asp Arg Va - #l Leu Glu Leu                      45          - #        50          - #        55                       - - Leu Arg Ser Gly Thr Asp Ile Asn Thr Cys As - #n Ala Asn Gly                          60      - #            65      - #            70                   - - Leu Asn Ala Leu His Leu Ala Ser Lys Glu Gl - #y His His Glu                              75  - #                80                                      - - Val Val Arg Glu Leu Leu Lys Arg Lys Ala As - #p Val Asp Ala              85                  - #90                  - #95                               - - Ala Thr Arg Lys Gly Asn Thr Ala Leu His Il - #e Ala Ser Leu                  100              - #   105              - #   110                          - - Ala Gly Gln Glu Leu Ile Val Thr Val Leu Va - #l Glu Asn Gly                      115          - #       120          - #       125                      - - Ala Asn Val Asn Val Gln Ser Leu Asn Gly Ph - #e Thr Pro Leu                          130      - #           135      - #           140                  - - Tyr Met Ala Ala Gln Glu Asn His Glu Ser Va - #l Val Arg Tyr                              145  - #               150                                     - - Leu Leu Ala His Asn Ala Asn Gln Ala Leu Se - #r Thr Glu Asp              155                 1 - #60                 1 - #65                            - - Gly Phe Thr Pro Leu Ala Val Ala Leu Gln Gl - #n Gly His Asp                  170              - #   175              - #   180                          - - Arg Val Val Ala Val Leu Leu Glu Asn Asp Th - #r Arg Gly Lys                      185          - #       190          - #       195                      - - Val Arg Leu Pro Ala Leu His Ile Ala Ala Ly - #s Lys Asp Asp                          200      - #           205      - #           210                  - - Thr Lys Ala Ala Thr Leu Leu Leu Gln Asn Gl - #u His Asn Ser                              215  - #               220                                     - - Asp Val Thr Ser Lys Ser Gly Phe Thr Pro Le - #u His Ile Ala              225                 2 - #30                 2 - #35                            - - Ala His Tyr Gly Asn Glu Asn Val Ala Gln Le - #u Leu Leu Glu                  240              - #   245              - #   250                          - - Lys Gly Ala Asn Val Asn Tyr Gln Ala Arg Hi - #s Asn Ile Ser                      255          - #       260          - #       265                      - - Pro Leu His Val Ala Thr Lys Trp Gly Arg Th - #r Asn Met Val                          270      - #           275      - #           280                  - - Ser Leu Leu Leu Ala His Gly Ala Val Ile As - #p Cys Arg Thr                              285  - #               290                                     - - Arg Asp Leu Leu Thr Pro Leu His Cys Ala Se - #r Arg Ser Gly              295                 3 - #00                 3 - #05                            - - His Asp Gln Val Val Asp Leu Leu Leu Glu Ly - #s Gly Ala Pro                  310              - #   315              - #   320                          - - Ile Ser Ala Lys Thr Lys Asn Gly Leu Ala Pr - #o Leu His Met                      325          - #       330          - #       335                      - - Ala Ala Gln Val Asp Asp Val Thr Val Asp Ty - #r Leu                                  340      - #           345                                         - -  - - (2) INFORMATION FOR SEQ ID NO:29:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1096 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #29:                         - - GTGAGATAGT CAACAGTAAC ATCATCCACC TGTGCTGCCA TATGTAAGGG  - #                  50                                                                         - - AGCCAAACCA TTTTTTGTCT TAGCACTGAT TGGAGCTCCT TTTTCAAGCA  - #                 100                                                                         - - ACAAATCAAC AACTTGATCA TGACCTGAAC GAGAAGCACA GTGTAATGGT  - #                 150                                                                         - - GTTAGTAAAT CACGTGTGCG ACAGTCAATT ACGGCCCCAT GAGCCAACAA  - #                 200                                                                         - - TAACGAAACC ATGTTTGTAC GACCCCATTT TGTTGCAACG TGTAACGGAC  - #                 250                                                                         - - TTATGTTATG TCTCGCTTGG TAATTCACAT TGGCTCCCTT TTCGAGTAGC  - #                 300                                                                         - - AGTTGTGCTA CGTTCTCATT TCCATAGTGA GCGGCGATAT GAAGCGGAGT  - #                 350                                                                         - - AAAGCCGCTT TTCGAAGTCA CATCCGAGTT ATGCTCATTT TGAAGTAATA  - #                 400                                                                         - - GCGTAGCTGC TTTCGTATCA TCTTTTTTAG CAGCAATATG CAGTGCTGGC  - #                 450                                                                         - - AAGCGCACTT TCCCGCGCGT GTCATTTTCA AGCAAAACAG CGACCACACG  - #                 500                                                                         - - ATCGTGACCT TGTTGCAAGG CAACTGCCAG TGGCGTAAAA CCGTCTTCTG  - #                 550                                                                         - - TACTTAAAGC TTGATTGGCA TTGTGGGCAA GAAGATAGCG TACAACAGAT  - #                 600                                                                         - - TCGTGATTTT CTTGTGCAGC CATGTAAAGT GGTGTAAAAC CGTTTAGTGA  - #                 650                                                                         - - TTGTACGTTA ACATTAGCAC CATTTTCAAC AAGTACTGTG ACGATTAGTT  - #                 700                                                                         - - CTTGTCCTGC CAATGATGCT ATATGTAACG CTGTGTTACC CTTTCTAGTG  - #                 750                                                                         - - GCAGCATCAA CATCTGCTTT TCTTTTCAGA AGTTCGCGGA CCACTTCATG  - #                 800                                                                         - - ATGACCTTCT TTGGAGGCCA GATGCAATGC ATTAAGGCCA TTCGCATTGC  - #                 850                                                                         - - ATGTGTTGAT ATCGGTGCCC GAACGAAGTA GTTCAAGTAC ACGATCCAAA  - #                 900                                                                         - - TTTCCAGCTC TTGCTGCTCG TAAAAAACTT GCACTGCTCT CACCTTTGTT  - #                 950                                                                         - - GGAATGTTGA CTGTTATCAT CAGGAATTTG TTGTTGATGT TGTGAATCTT  - #                1000                                                                         - - TTGGTTCTGC GGGCCAGCCA CTTCCCTCGA CTATAGGATT ACTCATCAAT  - #                1050                                                                         - - AGTTGAGTTA TATCAGTCAG CCGCCTCAAA CTTGGGTAAT TAAACC   - #                   1096                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:30:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1044 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #30:                         - - ATGAGTAATC CTATAGTCGA GGGAAGTGGC TGGCCCGCAG AACCAAAAGA  - #                  50                                                                         - - TTCACAACAT CAACAACAAA TTCCTGATGA TAACAGTCAA CATTCCAACA  - #                 100                                                                         - - AAGGTGAGAG CAGTGCAAGT TTTTTACGAG CAGCAAGAGC TGGAAATTTG  - #                 150                                                                         - - GATCGTGTAC TTGAACTACT TCGTTCGGGC ACCGATATCA ACACATGCAA  - #                 200                                                                         - - TGCGAATGGC CTTAATGCAT TGCATCTGGC CTCCAAAGAA GGTCATCATG  - #                 250                                                                         - - AAGTGGTCCG CGAACTTCTG AAAAGAAAAG CAGATGTTGA TGCTGCCACT  - #                 300                                                                         - - AGAAAGGGTA ACACAGCGTT ACATATAGCA TCATTGGCAG GACAAGAACT  - #                 350                                                                         - - AATCGTCACA GTACTTGTTG AAAATGGTGC TAATGTTAAC GTACAATCAC  - #                 400                                                                         - - TAAACGGTTT TACACCACTT TACATGGCTG CACAAGAAAA TCACGAATCT  - #                 450                                                                         - - GTTGTACGCT ATCTTCTTGC CCACAATGCC AATCAAGCTT TAAGTACAGA  - #                 500                                                                         - - AGACGGTTTT ACGCCACTGG CAGTTGCCTT GCAACAAGGT CACGATCGTG  - #                 550                                                                         - - TGGTCGCTGT TTTGCTTGAA AATGACACGC GCGGGAAAGT GCGCTTGCCA  - #                 600                                                                         - - GCACTGCATA TTGCTGCTAA AAAAGATGAT ACGAAAGCAG CTACGCTATT  - #                 650                                                                         - - ACTTCAAAAT GAGCATAACT CGGATGTGAC TTCGAAAAGC GGCTTTACTC  - #                 700                                                                         - - CGCTTCATAT CGCCGCTCAC TATGGAAATG AGAACGTAGC ACAACTGCTA  - #                 750                                                                         - - CTCGAAAAGG GAGCCAATGT GAATTACCAA GCGAGACATA ACATAAGTCC  - #                 800                                                                         - - GTTACACGTT GCAACAAAAT GGGGTCGTAC AAACATGGTT TCGTTATTGT  - #                 850                                                                         - - TGGCTCATGG GGCCGTAATT GACTGTCGCA CACGTGATTT ACTAACACCA  - #                 900                                                                         - - TTACACTGTG CTTCTCGTTC AGGTCATGAT CAAGTTGTTG ATTTGTTGCT  - #                 950                                                                         - - TGAAAAAGGA GCTCCAATCA GTGCTAAGAC AAAAAATGGT TTGGCTCCCT  - #                1000                                                                         - - TACATATGGC AGCACAGGTG GATGATGTTA CTGTTGACTA TCTC   - #                     104 - #4                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:31:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1044 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #31:                         - - GAGATAGTCA ACAGTAACAT CATCCACCTG TGCTGCCATA TGTAAGGGAG  - #                  50                                                                         - - CCAAACCATT TTTTGTCTTA GCACTGATTG GAGCTCCTTT TTCAAGCAAC  - #                 100                                                                         - - AAATCAACAA CTTGATCATG ACCTGAACGA GAAGCACAGT GTAATGGTGT  - #                 150                                                                         - - TAGTAAATCA CGTGTGCGAC AGTCAATTAC GGCCCCATGA GCCAACAATA  - #                 200                                                                         - - ACGAAACCAT GTTTGTACGA CCCCATTTTG TTGCAACGTG TAACGGACTT  - #                 250                                                                         - - ATGTTATGTC TCGCTTGGTA ATTCACATTG GCTCCCTTTT CGAGTAGCAG  - #                 300                                                                         - - TTGTGCTACG TTCTCATTTC CATAGTGAGC GGCGATATGA AGCGGAGTAA  - #                 350                                                                         - - AGCCGCTTTT CGAAGTCACA TCCGAGTTAT GCTCATTTTG AAGTAATAGC  - #                 400                                                                         - - GTAGCTGCTT TCGTATCATC TTTTTTAGCA GCAATATGCA GTGCTGGCAA  - #                 450                                                                         - - GCGCACTTTC CCGCGCGTGT CATTTTCAAG CAAAACAGCG ACCACACGAT  - #                 500                                                                         - - CGTGACCTTG TTGCAAGGCA ACTGCCAGTG GCGTAAAACC GTCTTCTGTA  - #                 550                                                                         - - CTTAAAGCTT GATTGGCATT GTGGGCAAGA AGATAGCGTA CAACAGATTC  - #                 600                                                                         - - GTGATTTTCT TGTGCAGCCA TGTAAAGTGG TGTAAAACCG TTTAGTGATT  - #                 650                                                                         - - GTACGTTAAC ATTAGCACCA TTTTCAACAA GTACTGTGAC GATTAGTTCT  - #                 700                                                                         - - TGTCCTGCCA ATGATGCTAT ATGTAACGCT GTGTTACCCT TTCTAGTGGC  - #                 750                                                                         - - AGCATCAACA TCTGCTTTTC TTTTCAGAAG TTCGCGGACC ACTTCATGAT  - #                 800                                                                         - - GACCTTCTTT GGAGGCCAGA TGCAATGCAT TAAGGCCATT CGCATTGCAT  - #                 850                                                                         - - GTGTTGATAT CGGTGCCCGA ACGAAGTAGT TCAAGTACAC GATCCAAATT  - #                 900                                                                         - - TCCAGCTCTT GCTGCTCGTA AAAAACTTGC ACTGCTCTCA CCTTTGTTGG  - #                 950                                                                         - - AATGTTGACT GTTATCATCA GGAATTTGTT GTTGATGTTG TGAATCTTTT  - #                1000                                                                         - - GGTTCTGCGG GCCAGCCACT TCCCTCGACT ATAGGATTAC TCAT   - #                     104 - #4                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:32:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  5503 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  51..5285                                              - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #32:                         - - GGTTTAATTA CCCAAGTTTG AGGCGGCTGA CTGATATAAC TCAACTATTG  - #                  50                                                                         - - ATG AGT AAT CCT ATA GTC GAG GGA AGT GGC TG - #G CCC GCA GAA                 - #  92                                                                    Met Ser Asn Pro Ile Val Glu Gly Ser Gly Tr - #p Pro Ala Glu                   1               5   - #               10                                       - - CCA AAA GAT TCA CAA CAT CAA CAA CAA ATT CC - #T GAT GAT AAC                 - # 134                                                                    Pro Lys Asp Ser Gln His Gln Gln Gln Ile Pr - #o Asp Asp Asn                   15                  - #20                  - #25                               - - AGT CAA CAT TCC AAC AAA GGT GAG AGC AGT GC - #A AGT TTT TTA                 - # 176                                                                    Ser Gln His Ser Asn Lys Gly Glu Ser Ser Al - #a Ser Phe Leu                   30                  - #35                  - #40                               - - CGA GCA GCA AGA GCT GGA AAT TTG GAT CGT GT - #A CTT GAA CTA                 - # 218                                                                    Arg Ala Ala Arg Ala Gly Asn Leu Asp Arg Va - #l Leu Glu Leu                   45                  - #50                  - #55                               - - CTT CGT TCG GGC ACC GAT ATC AAC ACA TGC AA - #T GCG AAT GGC                 - # 260                                                                    Leu Arg Ser Gly Thr Asp Ile Asn Thr Cys As - #n Ala Asn Gly                   60                  - #65                  - #70                               - - CTT AAT GCA TTG CAT CTG GCC TCC AAA GAA GG - #T CAT CAT GAA                 - # 302                                                                    Leu Asn Ala Leu His Leu Ala Ser Lys Glu Gl - #y His His Glu                   75                  - #80                                                      - - GTG GTC CGC GAA CTT CTG AAA AGA AAA GCA GA - #T GTT GAT GCT                 - # 344                                                                    Val Val Arg Glu Leu Leu Lys Arg Lys Ala As - #p Val Asp Ala                   85                  - #90                  - #95                               - - GCC ACT AGA AAG GGT AAC ACA GCG TTA CAT AT - #A GCA TCA TTG                 - # 386                                                                    Ala Thr Arg Lys Gly Asn Thr Ala Leu His Il - #e Ala Ser Leu                   100                 1 - #05                 1 - #10                            - - GCA GGA CAA GAA CTA ATC GTC ACA GTA CTT GT - #T GAA AAT GGT                 - # 428                                                                    Ala Gly Gln Glu Leu Ile Val Thr Val Leu Va - #l Glu Asn Gly                   115                 1 - #20                 1 - #25                            - - GCT AAT GTT AAC GTA CAA TCA CTA AAC GGT TT - #T ACA CCA CTT                 - # 470                                                                    Ala Asn Val Asn Val Gln Ser Leu Asn Gly Ph - #e Thr Pro Leu                   130                 1 - #35                 1 - #40                            - - TAC ATG GCT GCA CAA GAA AAT CAC GAA TCT GT - #T GTA CGC TAT                 - # 512                                                                    Tyr Met Ala Ala Gln Glu Asn His Glu Ser Va - #l Val Arg Tyr                   145                 1 - #50                                                    - - CTT CTT GCC CAC AAT GCC AAT CAA GCT TTA AG - #T ACA GAA GAC                 - # 554                                                                    Leu Leu Ala His Asn Ala Asn Gln Ala Leu Se - #r Thr Glu Asp                   155                 1 - #60                 1 - #65                            - - GGT TTT ACG CCA CTG GCA GTT GCC TTG CAA CA - #A GGT CAC GAT                 - # 596                                                                    Gly Phe Thr Pro Leu Ala Val Ala Leu Gln Gl - #n Gly His Asp                   170                 1 - #75                 1 - #80                            - - CGT GTG GTC GCT GTT TTG CTT GAA AAT GAC AC - #G CGC GGG AAA                 - # 638                                                                    Arg Val Val Ala Val Leu Leu Glu Asn Asp Th - #r Arg Gly Lys                   185                 1 - #90                 1 - #95                            - - GTG CGC TTG CCA GCA CTG CAT ATT GCT GCT AA - #A AAA GAT GAT                 - # 680                                                                    Val Arg Leu Pro Ala Leu His Ile Ala Ala Ly - #s Lys Asp Asp                   200                 2 - #05                 2 - #10                            - - ACG AAA GCA GCT ACG CTA TTA CTT CAA AAT GA - #G CAT AAC TCG                 - # 722                                                                    Thr Lys Ala Ala Thr Leu Leu Leu Gln Asn Gl - #u His Asn Ser                   215                 2 - #20                                                    - - GAT GTG ACT TCG AAA AGC GGC TTT ACT CCG CT - #T CAT ATC GCC                 - # 764                                                                    Asp Val Thr Ser Lys Ser Gly Phe Thr Pro Le - #u His Ile Ala                   225                 2 - #30                 2 - #35                            - - GCT CAC TAT GGA AAT GAG AAC GTA GCA CAA CT - #G CTA CTC GAA                 - # 806                                                                    Ala His Tyr Gly Asn Glu Asn Val Ala Gln Le - #u Leu Leu Glu                   240                 2 - #45                 2 - #50                            - - AAG GGA GCC AAT GTG AAT TAC CAA GCG AGA CA - #T AAC ATA AGT                 - # 848                                                                    Lys Gly Ala Asn Val Asn Tyr Gln Ala Arg Hi - #s Asn Ile Ser                   255                 2 - #60                 2 - #65                            - - CCG TTA CAC GTT GCA ACA AAA TGG GGT CGT AC - #A AAC ATG GTT                 - # 890                                                                    Pro Leu His Val Ala Thr Lys Trp Gly Arg Th - #r Asn Met Val                   270                 2 - #75                 2 - #80                            - - TCG TTA TTG TTG GCT CAT GGG GCC GTA ATT GA - #C TGT CGC ACA                 - # 932                                                                    Ser Leu Leu Leu Ala His Gly Ala Val Ile As - #p Cys Arg Thr                   285                 2 - #90                                                    - - CGT GAT TTA CTA ACA CCA TTA CAC TGT GCT TC - #T CGT TCA GGT                 - # 974                                                                    Arg Asp Leu Leu Thr Pro Leu His Cys Ala Se - #r Arg Ser Gly                   295                 3 - #00                 3 - #05                            - - CAT GAT CAA GTT GTT GAT TTG TTG CTT GAA AA - #A GGA GCT CCA                 - #1016                                                                    His Asp Gln Val Val Asp Leu Leu Leu Glu Ly - #s Gly Ala Pro                   310                 3 - #15                 3 - #20                            - - ATC AGT GCT AAG ACA AAA AAT GGT TTG GCT CC - #C TTA CAT ATG                 - #1058                                                                    Ile Ser Ala Lys Thr Lys Asn Gly Leu Ala Pr - #o Leu His Met                   325                 3 - #30                 3 - #35                            - - GCA GCA CAG GTG GAT GAT GTT ACT GTT GAC TA - #T CTC ACT CCT                 - #1100                                                                    Ala Ala Gln Val Asp Asp Val Thr Val Asp Ty - #r Leu Thr Pro                   340                 3 - #45                 3 - #50                            - - CTT CAT GTG GCT GCT CAT TGC GGA CAT GTC CG - #T GTC GCT AAA                 - #1142                                                                    Leu His Val Ala Ala His Cys Gly His Val Ar - #g Val Ala Lys                   355                 3 - #60                                                    - - CTT TTG CTG GAT CGT AAT GCT GAC CCG AAT GC - #T CGA GCT CTC                 - #1184                                                                    Leu Leu Leu Asp Arg Asn Ala Asp Pro Asn Al - #a Arg Ala Leu                   365                 3 - #70                 3 - #75                            - - AAT GGC TTC ACA CCG CTG CAT ATC GCT TGC AA - #A AAA AAT CGC                 - #1226                                                                    Asn Gly Phe Thr Pro Leu His Ile Ala Cys Ly - #s Lys Asn Arg                   380                 3 - #85                 3 - #90                            - - ATT AAA ATT GTC GAA CTG CTA CTG AAA TAC CA - #C GCT GCA ATC                 - #1268                                                                    Ile Lys Ile Val Glu Leu Leu Leu Lys Tyr Hi - #s Ala Ala Ile                   395                 4 - #00                 4 - #05                            - - GAA GCA ACT ACT GAA TCC GGT CTC TCA CCG CT - #G CAT GTC GCT                 - #1310                                                                    Glu Ala Thr Thr Glu Ser Gly Leu Ser Pro Le - #u His Val Ala                   410                 4 - #15                 4 - #20                            - - GCT TTT ATG GGT GCT ATA AAC ATT GTC ATC TA - #T TTA CTA CAA                 - #1352                                                                    Ala Phe Met Gly Ala Ile Asn Ile Val Ile Ty - #r Leu Leu Gln                   425                 4 - #30                                                    - - CAA GGT GCT AAT GCA GAT GTG GCT ACA GTA CG - #C GGT GAA ACG                 - #1394                                                                    Gln Gly Ala Asn Ala Asp Val Ala Thr Val Ar - #g Gly Glu Thr                   435                 4 - #40                 4 - #45                            - - CCT CTT CAT TTA GCT GCA CGA GCA AAC CAA AC - #G GAC ATT GTT                 - #1436                                                                    Pro Leu His Leu Ala Ala Arg Ala Asn Gln Th - #r Asp Ile Val                   450                 4 - #55                 4 - #60                            - - CGT GTT TTG GTG CGT AAT GGA GCA CAG GTG GA - #T GCT GCT GCT                 - #1478                                                                    Arg Val Leu Val Arg Asn Gly Ala Gln Val As - #p Ala Ala Ala                   465                 4 - #70                 4 - #75                            - - CGT GAA CTA CAA ACT CCA CTG CAC ATT GCA TC - #A CGT CTT GGT                 - #1520                                                                    Arg Glu Leu Gln Thr Pro Leu His Ile Ala Se - #r Arg Leu Gly                   480                 4 - #85                 4 - #90                            - - AAT ACC GAC ATC GTC ATT TTG TTG CTG CAG GC - #T AAT GCA TCA                 - #1562                                                                    Asn Thr Asp Ile Val Ile Leu Leu Leu Gln Al - #a Asn Ala Ser                   495                 5 - #00                                                    - - CCA AAT GCT GCC ACA AGA GAT CTT TAT ACT CC - #T CTT CAT ATT                 - #1604                                                                    Pro Asn Ala Ala Thr Arg Asp Leu Tyr Thr Pr - #o Leu His Ile                   505                 5 - #10                 5 - #15                            - - GCT GCC AAG GAG GGG CAA GAG GAA GTG GCA GC - #A ATA TTG ATG                 - #1646                                                                    Ala Ala Lys Glu Gly Gln Glu Glu Val Ala Al - #a Ile Leu Met                   520                 5 - #25                 5 - #30                            - - GAT CAT GGA ACC GAC AAG ACA CTG CTC ACG AA - #A AAG GGT TTT                 - #1688                                                                    Asp His Gly Thr Asp Lys Thr Leu Leu Thr Ly - #s Lys Gly Phe                   535                 5 - #40                 5 - #45                            - - ACG CCG TTG CAT TTA GCT GCT AAG TAT GGC AA - #T TTG CCG GTC                 - #1730                                                                    Thr Pro Leu His Leu Ala Ala Lys Tyr Gly As - #n Leu Pro Val                   550                 5 - #55                 5 - #60                            - - GCG AAA TCA TTG CTA GAA CGA GGA ACA CCG GT - #T GAC ATT GAA                 - #1772                                                                    Ala Lys Ser Leu Leu Glu Arg Gly Thr Pro Va - #l Asp Ile Glu                   565                 5 - #70                                                    - - GGC AAG AAT CAG GTA ACA CCT CTG CAT GTA GC - #G GCA CAT TAC                 - #1814                                                                    Gly Lys Asn Gln Val Thr Pro Leu His Val Al - #a Ala His Tyr                   575                 5 - #80                 5 - #85                            - - AAT AAC GAC AAG GTA GCA TTG TTA CTT CTA GA - #A AAT GGT GCT                 - #1856                                                                    Asn Asn Asp Lys Val Ala Leu Leu Leu Leu Gl - #u Asn Gly Ala                   590                 5 - #95                 6 - #00                            - - TCT GCA CAT GCC GCT GCC AAG AAT GGG TAC AC - #T CCT TTA CAT                 - #1898                                                                    Ser Ala His Ala Ala Ala Lys Asn Gly Tyr Th - #r Pro Leu His                   605                 6 - #10                 6 - #15                            - - ATT GCC GCG AAG AAG AAT CAG ATG GAT ATT GC - #T AGC ACT CTC                 - #1940                                                                    Ile Ala Ala Lys Lys Asn Gln Met Asp Ile Al - #a Ser Thr Leu                   620                 6 - #25                 6 - #30                            - - CTT CAT TAT AAG GCA AAT GCG AAT GCT GAA AG - #C AAA GCT GGC                 - #1982                                                                    Leu His Tyr Lys Ala Asn Ala Asn Ala Glu Se - #r Lys Ala Gly                   635                 6 - #40                                                    - - TTT ACA CCA CTT CAT CTT GCC GCC CAG GAG GG - #C CAT CGC GAA                 - #2024                                                                    Phe Thr Pro Leu His Leu Ala Ala Gln Glu Gl - #y His Arg Glu                   645                 6 - #50                 6 - #55                            - - ATG GCT GCG TTA TTA ATT GAA AAT GGA GCA AA - #A GTT GGA GCT                 - #2066                                                                    Met Ala Ala Leu Leu Ile Glu Asn Gly Ala Ly - #s Val Gly Ala                   660                 6 - #65                 6 - #70                            - - CAG GCA AGG AAT GGC TTG ACA CCA ATG CAT TT - #A TGT GCA CAG                 - #2108                                                                    Gln Ala Arg Asn Gly Leu Thr Pro Met His Le - #u Cys Ala Gln                   675                 6 - #80                 6 - #85                            - - GAG GAT CGT GTG AGC GTA GCA GAA GAA CTA GT - #G AAA GAA AAC                 - #2150                                                                    Glu Asp Arg Val Ser Val Ala Glu Glu Leu Va - #l Lys Glu Asn                   690                 6 - #95                 7 - #00                            - - GCA GCC ATT GAT CCC AAA ACG AAA GCA GGA TA - #T ACG CCG TTA                 - #2192                                                                    Ala Ala Ile Asp Pro Lys Thr Lys Ala Gly Ty - #r Thr Pro Leu                   705                 7 - #10                                                    - - CAT GTT GCT TGC CAT TTT GGA CAA ATA AAC AT - #G GTC CGT TTC                 - #2234                                                                    His Val Ala Cys His Phe Gly Gln Ile Asn Me - #t Val Arg Phe                   715                 7 - #20                 7 - #25                            - - TTG ATT GAG CAT GGC GCA CGA GTT TCA GTT AT - #T ACT CGT GCT                 - #2276                                                                    Leu Ile Glu His Gly Ala Arg Val Ser Val Il - #e Thr Arg Ala                   730                 7 - #35                 7 - #40                            - - TCC TAT ACT CCT CTG CAT CAA GCT GCT CAG CA - #A GGG CAT AAC                 - #2318                                                                    Ser Tyr Thr Pro Leu His Gln Ala Ala Gln Gl - #n Gly His Asn                   745                 7 - #50                 7 - #55                            - - AGT GTT GTA CGT TAC TTG TTG GAA CAT GGT GC - #A AGT CCA AAT                 - #2360                                                                    Ser Val Val Arg Tyr Leu Leu Glu His Gly Al - #a Ser Pro Asn                   760                 7 - #65                 7 - #70                            - - GTT CAT ACA TCG ACA GGA CAA ACT CCA TTA TC - #G ATT GCT GAA                 - #2402                                                                    Val His Thr Ser Thr Gly Gln Thr Pro Leu Se - #r Ile Ala Glu                   775                 7 - #80                                                    - - CGT CTA GGG TAT GTA TCC GTG GTT GAA GCG CT - #T AAA ACA ATT                 - #2444                                                                    Arg Leu Gly Tyr Val Ser Val Val Glu Ala Le - #u Lys Thr Ile                   785                 7 - #90                 7 - #95                            - - ACC GAG ACT ACT GTG ATA ACG GAG ACC ACA AC - #C GTT ACT GAA                 - #2486                                                                    Thr Glu Thr Thr Val Ile Thr Glu Thr Thr Th - #r Val Thr Glu                   800                 8 - #05                 8 - #10                            - - GAA AGA TAT AAA CCT CAG AAT CCC GAA GCA AT - #G AAT GAA ACC                 - #2528                                                                    Glu Arg Tyr Lys Pro Gln Asn Pro Glu Ala Me - #t Asn Glu Thr                   815                 8 - #20                 8 - #25                            - - ATG TTT TCC GAT TCC GAA GAT GAA GGT GAA GA - #T AAT CAG ATC                 - #2570                                                                    Met Phe Ser Asp Ser Glu Asp Glu Gly Glu As - #p Asn Gln Ile                   830                 8 - #35                 8 - #40                            - - ACA GCC AAT GCT CAT GCT CAT GAT TTC TCA GA - #A AGC CTC ACA                 - #2612                                                                    Thr Ala Asn Ala His Ala His Asp Phe Ser Gl - #u Ser Leu Thr                   845                 8 - #50                                                    - - AAA GGT TTG CAC GAT TCA ACT GGT GTA CAT TT - #G ATT CAT GCC                 - #2654                                                                    Lys Gly Leu His Asp Ser Thr Gly Val His Le - #u Ile His Ala                   855                 8 - #60                 8 - #65                            - - ACA GAA CCG ACA TTG TCA CGA AGT CCG GAA GT - #G GAA GGT ACG                 - #2696                                                                    Thr Glu Pro Thr Leu Ser Arg Ser Pro Glu Va - #l Glu Gly Thr                   870                 8 - #75                 8 - #80                            - - GAT GGC GAT TTG GAT GCC TTA ATT CGT AAA GC - #A CAA CAT GAA                 - #2738                                                                    Asp Gly Asp Leu Asp Ala Leu Ile Arg Lys Al - #a Gln His Glu                   885                 8 - #90                 8 - #95                            - - CCA ATT ACT ACA GCG ATG GCC GAT CCT TCC TT - #A GAT GCA TCG                 - #2780                                                                    Pro Ile Thr Thr Ala Met Ala Asp Pro Ser Le - #u Asp Ala Ser                   900                 9 - #05                 9 - #10                            - - CTT CCT GAC AAT GTT ACG ATA ATG AGA ACT AC - #C ATG CAA CCT                 - #2822                                                                    Leu Pro Asp Asn Val Thr Ile Met Arg Thr Th - #r Met Gln Pro                   915                 9 - #20                                                    - - AGT TTT TTA ATT TCG TTT ATG GTG GAT GCA CG - #T GGA GGA GCA                 - #2864                                                                    Ser Phe Leu Ile Ser Phe Met Val Asp Ala Ar - #g Gly Gly Ala                   925                 9 - #30                 9 - #35                            - - ATG CGT GGT TGT AGG CAT TCC GGT GTC AGA AT - #C ATT ATA CCA                 - #2906                                                                    Met Arg Gly Cys Arg His Ser Gly Val Arg Il - #e Ile Ile Pro                   940                 9 - #45                 9 - #50                            - - CCG AGG AAA GCG CCG CAA CCT ACA CGG GTC AC - #A TGC AGA TAC                 - #2948                                                                    Pro Arg Lys Ala Pro Gln Pro Thr Arg Val Th - #r Cys Arg Tyr                   955                 9 - #60                 9 - #65                            - - CTT GGA AAG GAC AAG TTA GCG CAT CCA CCA CC - #A TTA AGT GAA                 - #2990                                                                    Leu Gly Lys Asp Lys Leu Ala His Pro Pro Pr - #o Leu Ser Glu                   970                 9 - #75                 9 - #80                            - - GGT GAA GCG CTC GCN TCA CGT ATA CTT GAA AT - #G GCA CCA CAT                 - #3032                                                                    Gly Glu Ala Leu Ala Ser Arg Ile Leu Glu Me - #t Ala Pro His                   985                 9 - #90                                                    - - GGA GCA AAA TTC TTA GGC CCT GTT ATA TTG GA - #A GTA CCA CAT                 - #3074                                                                    Gly Ala Lys Phe Leu Gly Pro Val Ile Leu Gl - #u Val Pro His                   995                 1 - #000                1005                               - - TTT GCA TCA CTT CGT GGA CGA GAG AGA GAG AT - #T GTC ATT TTG                 - #3116                                                                    Phe Ala Ser Leu Arg Gly Arg Glu Arg Glu Il - #e Val Ile Leu                   1010                1015 - #                1020                               - - CGT TCT GAT GAT GGG CAG CAT TGG AAA GAG CA - #T CAG CTT GAA                 - #3158                                                                    Arg Ser Asp Asp Gly Gln His Trp Lys Glu Hi - #s Gln Leu Glu                   1025                1030 - #                1035                               - - GCA ACA GAA GAT GCT GTA CAA GAG GTG CTC AA - #T GAA TCG TTT                 - #3200                                                                    Ala Thr Glu Asp Ala Val Gln Glu Val Leu As - #n Glu Ser Phe                   1040                1045 - #                1050                               - - GAT GCA GAA GAG TTG TCG CAA CTT GAT GAT TT - #G CAT ACA TCA                 - #3242                                                                    Asp Ala Glu Glu Leu Ser Gln Leu Asp Asp Le - #u His Thr Ser                   1055                1060                                                       - - CGG ATT ACG CGT ATC CTG ACC AAT GAT TTC CC - #A ATG TAT TTC                 - #3284                                                                    Arg Ile Thr Arg Ile Leu Thr Asn Asp Phe Pr - #o Met Tyr Phe                   1065                1070 - #                1075                               - - GCG GTC GTT ACT CGT GTG CGG CAA GAA GTG CA - #C TGT GTT GGT                 - #3326                                                                    Ala Val Val Thr Arg Val Arg Gln Glu Val Hi - #s Cys Val Gly                   1080                1085 - #                1090                               - - CCA GAA GGT GGT GTA ATA CTC TCT TCA GTT GT - #T CCT CAT GTG                 - #3368                                                                    Pro Glu Gly Gly Val Ile Leu Ser Ser Val Va - #l Pro His Val                   1095                1100 - #                1105                               - - CAG GCC ATA TTT CCG GAT GGT TCC TTG ACT AA - #G ACG ATC AAA                 - #3410                                                                    Gln Ala Ile Phe Pro Asp Gly Ser Leu Thr Ly - #s Thr Ile Lys                   1110                1115 - #                1120                               - - GTA TCT GTG CAA GCC CAG CCA GTT CCA CAA GA - #G ATA GTC ACT                 - #3452                                                                    Val Ser Val Gln Ala Gln Pro Val Pro Gln Gl - #u Ile Val Thr                   1125                1130                                                       - - CGT TTA CAT GGG AAT AGA GTC GCT GTT TCT CC - #A ATT GTA ACT                 - #3494                                                                    Arg Leu His Gly Asn Arg Val Ala Val Ser Pr - #o Ile Val Thr                   1135                1140 - #                1145                               - - GTT GAA CCG CGT CGT CGC AAA TTC CAT AAG CC - #C ATA ACG CTG                 - #3536                                                                    Val Glu Pro Arg Arg Arg Lys Phe His Lys Pr - #o Ile Thr Leu                   1150                1155 - #                1160                               - - TGC ATA CCA TTG CCA CAA AGC TCA AAT AAA GG - #A ATG TTA ACA                 - #3578                                                                    Cys Ile Pro Leu Pro Gln Ser Ser Asn Lys Gl - #y Met Leu Thr                   1165                1170 - #                1175                               - - CAA TAT AGT GGC CAA CCA GGA CAG GAA CCA CC - #G ACG CTG CGT                 - #3620                                                                    Gln Tyr Ser Gly Gln Pro Gly Gln Glu Pro Pr - #o Thr Leu Arg                   1180                1185 - #                1190                               - - TTA CTC TGC AGT AAA ACT GGA GGT TCT TCT CC - #T GCA CAG TGG                 - #3662                                                                    Leu Leu Cys Ser Lys Thr Gly Gly Ser Ser Pr - #o Ala Gln Trp                   1195                1200                                                       - - GAA GAT ATT ACT GGA ACT ACC CAG TTA ACA TT - #T ACT GGT GAG                 - #3704                                                                    Glu Asp Ile Thr Gly Thr Thr Gln Leu Thr Ph - #e Thr Gly Glu                   1205                1210 - #                1215                               - - GAC GTT TCA TTT ACA ACT ACG GTT TCT GCT CG - #A TTT TGG TTG                 - #3746                                                                    Asp Val Ser Phe Thr Thr Thr Val Ser Ala Ar - #g Phe Trp Leu                   1220                1225 - #                1230                               - - ATG GAT TGC CAA ACT CCG CGA GAT GCG GCA CG - #A ATG GCA CAA                 - #3788                                                                    Met Asp Cys Gln Thr Pro Arg Asp Ala Ala Ar - #g Met Ala Gln                   1235                1240 - #                1245                               - - GAA GTT TAC AAT GAA GCA ATT GCA GTT CCT TA - #T ATG GCT AAA                 - #3830                                                                    Glu Val Tyr Asn Glu Ala Ile Ala Val Pro Ty - #r Met Ala Lys                   1250                1255 - #                1260                               - - TTT CTT ATT TTT GCT CGA CGA ACT TTT CCT GC - #C GAA GGA CAG                 - #3872                                                                    Phe Leu Ile Phe Ala Arg Arg Thr Phe Pro Al - #a Glu Gly Gln                   1265                1270                                                       - - TTG AGA TTG TTT TGT ATG ACT GAT GAT CGG GA - #A GAT AAA ACC                 - #3914                                                                    Leu Arg Leu Phe Cys Met Thr Asp Asp Arg Gl - #u Asp Lys Thr                   1275                1280 - #                1285                               - - CTG GAA AAA CAA GAA CGT TTC ATT GAA ATT GC - #G AAA TCG AAA                 - #3956                                                                    Leu Glu Lys Gln Glu Arg Phe Ile Glu Ile Al - #a Lys Ser Lys                   1290                1295 - #                1300                               - - GAT GTA GAA GTC TTA AGT GGG CGA CAT CAG TT - #T TTG GAA TTT                 - #3998                                                                    Asp Val Glu Val Leu Ser Gly Arg His Gln Ph - #e Leu Glu Phe                   1305                1310 - #                1315                               - - TCT GGA AAT CTT CTT CCA ATA ACC AAG AGT GG - #T GAC CAA CTT                 - #4040                                                                    Ser Gly Asn Leu Leu Pro Ile Thr Lys Ser Gl - #y Asp Gln Leu                   1320                1325 - #                1330                               - - TCT CTT TAT TTT CTA CCA TTC CAA GAA AAT CG - #T CTT GCT TTC                 - #4082                                                                    Ser Leu Tyr Phe Leu Pro Phe Gln Glu Asn Ar - #g Leu Ala Phe                   1335                1340                                                       - - ATG GTA AAG ATA CGC ACT CAC ACG GAC AAC GA - #A ACT GCA GCT                 - #4124                                                                    Met Val Lys Ile Arg Thr His Thr Asp Asn Gl - #u Thr Ala Ala                   1345                1350 - #                1355                               - - GAT GGC CGG ATA GTA TTT ATG AAA GAA CCA AA - #A TTG AGA GCC                 - #4166                                                                    Asp Gly Arg Ile Val Phe Met Lys Glu Pro Ly - #s Leu Arg Ala                   1360                1365 - #                1370                               - - GAA AAT TTA CCT CCG CAG ACG CCA GTG TGT AC - #T CTT GCA ATC                 - #4208                                                                    Glu Asn Leu Pro Pro Gln Thr Pro Val Cys Th - #r Leu Ala Ile                   1375                1380 - #                1385                               - - ACT CTT CCG GAA TAC ACT GGG CCG GAG CCG AT - #G GTT TCC AAA                 - #4250                                                                    Thr Leu Pro Glu Tyr Thr Gly Pro Glu Pro Me - #t Val Ser Lys                   1390                1395 - #                1400                               - - AAA CTC TTC TAT TCG GAA GCT TCT TTG ACT GA - #G AAA TAC GTT                 - #4292                                                                    Lys Leu Phe Tyr Ser Glu Ala Ser Leu Thr Gl - #u Lys Tyr Val                   1405                1410                                                       - - GGA GCT TTC CAT GAA ACT GCT GAA CCT GAT AA - #C TTG CCA CTA                 - #4334                                                                    Gly Ala Phe His Glu Thr Ala Glu Pro Asp As - #n Leu Pro Leu                   1415                1420 - #                1425                               - - GCA CAT GTT GCA CTA TTA ATT GGC GCT GAT TG - #G CAT CGG TTA                 - #4376                                                                    Ala His Val Ala Leu Leu Ile Gly Ala Asp Tr - #p His Arg Leu                   1430                1435 - #                1440                               - - GCT CGA GCG CTT GAA GTA CCT GAT ATT GAT AT - #A CGA CAA GTT                 - #4418                                                                    Ala Arg Ala Leu Glu Val Pro Asp Ile Asp Il - #e Arg Gln Val                   1445                1450 - #                1455                               - - CGA CAT CAA CTA GTT GGT CTT GAA GCA GTC AC - #T ATT CTA CGT                 - #4460                                                                    Arg His Gln Leu Val Gly Leu Glu Ala Val Th - #r Ile Leu Arg                   1460                1465 - #                1470                               - - ATT TGG ATA TTT TTG AAG AAA GAA CAA GCT AC - #G CCC GTT GCT                 - #4502                                                                    Ile Trp Ile Phe Leu Lys Lys Glu Gln Ala Th - #r Pro Val Ala                   1475                1480                                                       - - TTG CGA TCA GCA TTG CAG CGA ATA GGA CGT GA - #T GAT GTT GTA                 - #4544                                                                    Leu Arg Ser Ala Leu Gln Arg Ile Gly Arg As - #p Asp Val Val                   1485                1490 - #                1495                               - - CGA GAA ATG GAT CGA GCT GAA AAG CTA GAT GG - #T TTA GAA GGA                 - #4586                                                                    Arg Glu Met Asp Arg Ala Glu Lys Leu Asp Gl - #y Leu Glu Gly                   1500                1505 - #                1510                               - - ACA CCT GTA TCG CAT ATT TCT GGA CCC TCA AT - #A ACT CTG TCA                 - #4628                                                                    Thr Pro Val Ser His Ile Ser Gly Pro Ser Il - #e Thr Leu Ser                   1515                1520 - #                1525                               - - TCT ACT TTG CTA GAG GTA GCA GGC GAC AGA CG - #T CGT CAC GCC                 - #4670                                                                    Ser Thr Leu Leu Glu Val Ala Gly Asp Arg Ar - #g Arg His Ala                   1530                1535 - #                1540                               - - GAG GTA ACA ATG GCG CAA CAG CGA TTG GCA CA - #A GAA CCG TTT                 - #4712                                                                    Glu Val Thr Met Ala Gln Gln Arg Leu Ala Gl - #n Glu Pro Phe                   1545                1550                                                       - - TTT CAG CAA GTA GGG TAT AAT GGG ACA CCT GG - #A GAT CCA GAA                 - #4754                                                                    Phe Gln Gln Val Gly Tyr Asn Gly Thr Pro Gl - #y Asp Pro Glu                   1555                1560 - #                1565                               - - GAA CCC AAA GAA CAG TCA TTC CAC GAA GAG GA - #A GAG GAA GTT                 - #4796                                                                    Glu Pro Lys Glu Gln Ser Phe His Glu Glu Gl - #u Glu Glu Val                   1570                1575 - #                1580                               - - GCA GTT TCA GAA ATT CGA ACA GTT GTG CGC AC - #T GAA CGA CAT                 - #4838                                                                    Ala Val Ser Glu Ile Arg Thr Val Val Arg Th - #r Glu Arg His                   1585                1590 - #                1595                               - - GTG CAT GAT TCG GAA AAT GGT CCT ATT GTG GA - #A GAG CGT ACA                 - #4880                                                                    Val His Asp Ser Glu Asn Gly Pro Ile Val Gl - #u Glu Arg Thr                   1600                1605 - #                1610                               - - ATA ACA ACT ACG TAT GAG GAT GAT GTT GCT GT - #A AAC GAA GAA                 - #4922                                                                    Ile Thr Thr Thr Tyr Glu Asp Asp Val Ala Va - #l Asn Glu Glu                   1615                1620                                                       - - GAA ATT GTT GAC AAA ATA GTG CCT CTC AAC GA - #A GAG GAG CAA                 - #4964                                                                    Glu Ile Val Asp Lys Ile Val Pro Leu Asn Gl - #u Glu Glu Gln                   1625                1630 - #                1635                               - - GAA AAA TGG GAT CGA ATG GTT CGA GAA GTG GA - #A ATG AAT TTT                 - #5006                                                                    Glu Lys Trp Asp Arg Met Val Arg Glu Val Gl - #u Met Asn Phe                   1640                1645 - #                1650                               - - GAG CAA CAA GAA ACA TCA AAA GAA GGA ACG TT - #T GGT TGT CAG                 - #5048                                                                    Glu Gln Gln Glu Thr Ser Lys Glu Gly Thr Ph - #e Gly Cys Gln                   1655                1660 - #                1665                               - - ACA ACA CAT GAG AAA GAA AAA GAT GAT GAT GG - #T GGC AGT CTG                 - #5090                                                                    Thr Thr His Glu Lys Glu Lys Asp Asp Asp Gl - #y Gly Ser Leu                   1670                1675 - #                1680                               - - AAG ACG ACA ATG AAA GAT AGT CAC GTA AGG CA - #G ATT TTC TTC                 - #5132                                                                    Lys Thr Thr Met Lys Asp Ser His Val Arg Gl - #n Ile Phe Phe                   1685                1690                                                       - - GAT GGA GGT GAG ACA TCC GCT AAT GAA ACA GG - #A TTA AGT AGC                 - #5174                                                                    Asp Gly Gly Glu Thr Ser Ala Asn Glu Thr Gl - #y Leu Ser Ser                   1695                1700 - #                1705                               - - GGG GAT GCA GAC ACT ATT ATG ACT CCA ACG AC - #A AAG GAG GAT                 - #5216                                                                    Gly Asp Ala Asp Thr Ile Met Thr Pro Thr Th - #r Lys Glu Asp                   1710                1715 - #                1720                               - - AAT CAT GTT ATA GAC GTA ATG GAG GAA AGG CG - #A ACT GAT GAA                 - #5258                                                                    Asn His Val Ile Asp Val Met Glu Glu Arg Ar - #g Thr Asp Glu                   1725                1730 - #                1735                               - - GAG GCC AAA GGG CAA AGC GTT CAT GAA TAA TC - #TGGATCCA                    - #  5298                                                                    Glu Ala Lys Gly Gln Ser Val His Glu                                           1740                1745                                                       - - CAAATTGATT TAAATCGCAA TCTCGCACAT GCCTATGTTG CTAATATTTA  - #                5348                                                                         - - ATGAAATTTT TCAAAGCAAT AATTTGAATG CTGTTTGGGC TTCCCATATT  - #                5398                                                                         - - GTTAAAGCGT TTTCCATCGT CCATTCACTT TTTGTTTTTG CTGTAGTCTG  - #                5448                                                                         - - TAACTGCTAC TCTTGATAAA TTTGCTCCAG TAAAAAAAAA AAAAAAAAAA  - #                5498                                                                         - - AAAAA                 - #                  - #                  - #              5503                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:33:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1745 am - #ino acids                                             (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #33:                         - - Met Ser Asn Pro Ile Val Glu Gly Ser Gly Tr - #p Pro Ala Glu               1               5  - #                10                                      - - Pro Lys Asp Ser Gln His Gln Gln Gln Ile Pr - #o Asp Asp Asn              15                  - #20                  - #25                               - - Ser Gln His Ser Asn Lys Gly Glu Ser Ser Al - #a Ser Phe Leu                  30              - #    35              - #    40                           - - Arg Ala Ala Arg Ala Gly Asn Leu Asp Arg Va - #l Leu Glu Leu                      45          - #        50          - #        55                       - - Leu Arg Ser Gly Thr Asp Ile Asn Thr Cys As - #n Ala Asn Gly                          60      - #            65      - #            70                   - - Leu Asn Ala Leu His Leu Ala Ser Lys Glu Gl - #y His His Glu                              75  - #                80                                      - - Val Val Arg Glu Leu Leu Lys Arg Lys Ala As - #p Val Asp Ala              85                  - #90                  - #95                               - - Ala Thr Arg Lys Gly Asn Thr Ala Leu His Il - #e Ala Ser Leu                  100              - #   105              - #   110                          - - Ala Gly Gln Glu Leu Ile Val Thr Val Leu Va - #l Glu Asn Gly                      115          - #       120          - #       125                      - - Ala Asn Val Asn Val Gln Ser Leu Asn Gly Ph - #e Thr Pro Leu                          130      - #           135      - #           140                  - - Tyr Met Ala Ala Gln Glu Asn His Glu Ser Va - #l Val Arg Tyr                              145  - #               150                                     - - Leu Leu Ala His Asn Ala Asn Gln Ala Leu Se - #r Thr Glu Asp              155                 1 - #60                 1 - #65                            - - Gly Phe Thr Pro Leu Ala Val Ala Leu Gln Gl - #n Gly His Asp                  170              - #   175              - #   180                          - - Arg Val Val Ala Val Leu Leu Glu Asn Asp Th - #r Arg Gly Lys                      185          - #       190          - #       195                      - - Val Arg Leu Pro Ala Leu His Ile Ala Ala Ly - #s Lys Asp Asp                          200      - #           205      - #           210                  - - Thr Lys Ala Ala Thr Leu Leu Leu Gln Asn Gl - #u His Asn Ser                              215  - #               220                                     - - Asp Val Thr Ser Lys Ser Gly Phe Thr Pro Le - #u His Ile Ala              225                 2 - #30                 2 - #35                            - - Ala His Tyr Gly Asn Glu Asn Val Ala Gln Le - #u Leu Leu Glu                  240              - #   245              - #   250                          - - Lys Gly Ala Asn Val Asn Tyr Gln Ala Arg Hi - #s Asn Ile Ser                      255          - #       260          - #       265                      - - Pro Leu His Val Ala Thr Lys Trp Gly Arg Th - #r Asn Met Val                          270      - #           275      - #           280                  - - Ser Leu Leu Leu Ala His Gly Ala Val Ile As - #p Cys Arg Thr                              285  - #               290                                     - - Arg Asp Leu Leu Thr Pro Leu His Cys Ala Se - #r Arg Ser Gly              295                 3 - #00                 3 - #05                            - - His Asp Gln Val Val Asp Leu Leu Leu Glu Ly - #s Gly Ala Pro                  310              - #   315              - #   320                          - - Ile Ser Ala Lys Thr Lys Asn Gly Leu Ala Pr - #o Leu His Met                      325          - #       330          - #       335                      - - Ala Ala Gln Val Asp Asp Val Thr Val Asp Ty - #r Leu Thr Pro                          340      - #           345      - #           350                  - - Leu His Val Ala Ala His Cys Gly His Val Ar - #g Val Ala Lys                              355  - #               360                                     - - Leu Leu Leu Asp Arg Asn Ala Asp Pro Asn Al - #a Arg Ala Leu              365                 3 - #70                 3 - #75                            - - Asn Gly Phe Thr Pro Leu His Ile Ala Cys Ly - #s Lys Asn Arg                  380              - #   385              - #   390                          - - Ile Lys Ile Val Glu Leu Leu Leu Lys Tyr Hi - #s Ala Ala Ile                      395          - #       400          - #       405                      - - Glu Ala Thr Thr Glu Ser Gly Leu Ser Pro Le - #u His Val Ala                          410      - #           415      - #           420                  - - Ala Phe Met Gly Ala Ile Asn Ile Val Ile Ty - #r Leu Leu Gln                              425  - #               430                                     - - Gln Gly Ala Asn Ala Asp Val Ala Thr Val Ar - #g Gly Glu Thr              435                 4 - #40                 4 - #45                            - - Pro Leu His Leu Ala Ala Arg Ala Asn Gln Th - #r Asp Ile Val                  450              - #   455              - #   460                          - - Arg Val Leu Val Arg Asn Gly Ala Gln Val As - #p Ala Ala Ala                      465          - #       470          - #       475                      - - Arg Glu Leu Gln Thr Pro Leu His Ile Ala Se - #r Arg Leu Gly                          480      - #           485      - #           490                  - - Asn Thr Asp Ile Val Ile Leu Leu Leu Gln Al - #a Asn Ala Ser                              495  - #               500                                     - - Pro Asn Ala Ala Thr Arg Asp Leu Tyr Thr Pr - #o Leu His Ile              505                 5 - #10                 5 - #15                            - - Ala Ala Lys Glu Gly Gln Glu Glu Val Ala Al - #a Ile Leu Met                  520              - #   525              - #   530                          - - Asp His Gly Thr Asp Lys Thr Leu Leu Thr Ly - #s Lys Gly Phe                      535          - #       540          - #       545                      - - Thr Pro Leu His Leu Ala Ala Lys Tyr Gly As - #n Leu Pro Val                          550      - #           555      - #           560                  - - Ala Lys Ser Leu Leu Glu Arg Gly Thr Pro Va - #l Asp Ile Glu                              565  - #               570                                     - - Gly Lys Asn Gln Val Thr Pro Leu His Val Al - #a Ala His Tyr              575                 5 - #80                 5 - #85                            - - Asn Asn Asp Lys Val Ala Leu Leu Leu Leu Gl - #u Asn Gly Ala                  590              - #   595              - #   600                          - - Ser Ala His Ala Ala Ala Lys Asn Gly Tyr Th - #r Pro Leu His                      605          - #       610          - #       615                      - - Ile Ala Ala Lys Lys Asn Gln Met Asp Ile Al - #a Ser Thr Leu                          620      - #           625      - #           630                  - - Leu His Tyr Lys Ala Asn Ala Asn Ala Glu Se - #r Lys Ala Gly                              635  - #               640                                     - - Phe Thr Pro Leu His Leu Ala Ala Gln Glu Gl - #y His Arg Glu              645                 6 - #50                 6 - #55                            - - Met Ala Ala Leu Leu Ile Glu Asn Gly Ala Ly - #s Val Gly Ala                  660              - #   665              - #   670                          - - Gln Ala Arg Asn Gly Leu Thr Pro Met His Le - #u Cys Ala Gln                      675          - #       680          - #       685                      - - Glu Asp Arg Val Ser Val Ala Glu Glu Leu Va - #l Lys Glu Asn                          690      - #           695      - #           700                  - - Ala Ala Ile Asp Pro Lys Thr Lys Ala Gly Ty - #r Thr Pro Leu                              705  - #               710                                     - - His Val Ala Cys His Phe Gly Gln Ile Asn Me - #t Val Arg Phe              715                 7 - #20                 7 - #25                            - - Leu Ile Glu His Gly Ala Arg Val Ser Val Il - #e Thr Arg Ala                  730              - #   735              - #   740                          - - Ser Tyr Thr Pro Leu His Gln Ala Ala Gln Gl - #n Gly His Asn                      745          - #       750          - #       755                      - - Ser Val Val Arg Tyr Leu Leu Glu His Gly Al - #a Ser Pro Asn                          760      - #           765      - #           770                  - - Val His Thr Ser Thr Gly Gln Thr Pro Leu Se - #r Ile Ala Glu                              775  - #               780                                     - - Arg Leu Gly Tyr Val Ser Val Val Glu Ala Le - #u Lys Thr Ile              785                 7 - #90                 7 - #95                            - - Thr Glu Thr Thr Val Ile Thr Glu Thr Thr Th - #r Val Thr Glu                  800              - #   805              - #   810                          - - Glu Arg Tyr Lys Pro Gln Asn Pro Glu Ala Me - #t Asn Glu Thr                      815          - #       820          - #       825                      - - Met Phe Ser Asp Ser Glu Asp Glu Gly Glu As - #p Asn Gln Ile                          830      - #           835      - #           840                  - - Thr Ala Asn Ala His Ala His Asp Phe Ser Gl - #u Ser Leu Thr                              845  - #               850                                     - - Lys Gly Leu His Asp Ser Thr Gly Val His Le - #u Ile His Ala              855                 8 - #60                 8 - #65                            - - Thr Glu Pro Thr Leu Ser Arg Ser Pro Glu Va - #l Glu Gly Thr                  870              - #   875              - #   880                          - - Asp Gly Asp Leu Asp Ala Leu Ile Arg Lys Al - #a Gln His Glu                      885          - #       890          - #       895                      - - Pro Ile Thr Thr Ala Met Ala Asp Pro Ser Le - #u Asp Ala Ser                          900      - #           905      - #           910                  - - Leu Pro Asp Asn Val Thr Ile Met Arg Thr Th - #r Met Gln Pro                              915  - #               920                                     - - Ser Phe Leu Ile Ser Phe Met Val Asp Ala Ar - #g Gly Gly Ala              925                 9 - #30                 9 - #35                            - - Met Arg Gly Cys Arg His Ser Gly Val Arg Il - #e Ile Ile Pro                  940              - #   945              - #   950                          - - Pro Arg Lys Ala Pro Gln Pro Thr Arg Val Th - #r Cys Arg Tyr                      955          - #       960          - #       965                      - - Leu Gly Lys Asp Lys Leu Ala His Pro Pro Pr - #o Leu Ser Glu                          970      - #           975      - #           980                  - - Gly Glu Ala Leu Ala Ser Arg Ile Leu Glu Me - #t Ala Pro His                              985  - #               990                                     - - Gly Ala Lys Phe Leu Gly Pro Val Ile Leu Gl - #u Val Pro His              995                 1 - #000                1005                               - - Phe Ala Ser Leu Arg Gly Arg Glu Arg Glu Il - #e Val Ile Leu                  1010             - #   1015              - #  1020                         - - Arg Ser Asp Asp Gly Gln His Trp Lys Glu Hi - #s Gln Leu Glu                      1025         - #       1030          - #      1035                     - - Ala Thr Glu Asp Ala Val Gln Glu Val Leu As - #n Glu Ser Phe                          1040     - #           1045      - #          1050                 - - Asp Ala Glu Glu Leu Ser Gln Leu Asp Asp Le - #u His Thr Ser                              1055 - #               1060                                    - - Arg Ile Thr Arg Ile Leu Thr Asn Asp Phe Pr - #o Met Tyr Phe              1065                1070 - #                1075                               - - Ala Val Val Thr Arg Val Arg Gln Glu Val Hi - #s Cys Val Gly                  1080             - #   1085              - #  1090                         - - Pro Glu Gly Gly Val Ile Leu Ser Ser Val Va - #l Pro His Val                      1095         - #       1100          - #      1105                     - - Gln Ala Ile Phe Pro Asp Gly Ser Leu Thr Ly - #s Thr Ile Lys                          1110     - #           1115      - #          1120                 - - Val Ser Val Gln Ala Gln Pro Val Pro Gln Gl - #u Ile Val Thr                              1125 - #               1130                                    - - Arg Leu His Gly Asn Arg Val Ala Val Ser Pr - #o Ile Val Thr              1135                1140 - #                1145                               - - Val Glu Pro Arg Arg Arg Lys Phe His Lys Pr - #o Ile Thr Leu                  1150             - #   1155              - #  1160                         - - Cys Ile Pro Leu Pro Gln Ser Ser Asn Lys Gl - #y Met Leu Thr                      1165         - #       1170          - #      1175                     - - Gln Tyr Ser Gly Gln Pro Gly Gln Glu Pro Pr - #o Thr Leu Arg                          1180     - #           1185      - #          1190                 - - Leu Leu Cys Ser Lys Thr Gly Gly Ser Ser Pr - #o Ala Gln Trp                              1195 - #               1200                                    - - Glu Asp Ile Thr Gly Thr Thr Gln Leu Thr Ph - #e Thr Gly Glu              1205                1210 - #                1215                               - - Asp Val Ser Phe Thr Thr Thr Val Ser Ala Ar - #g Phe Trp Leu                  1220             - #   1225              - #  1230                         - - Met Asp Cys Gln Thr Pro Arg Asp Ala Ala Ar - #g Met Ala Gln                      1235         - #       1240          - #      1245                     - - Glu Val Tyr Asn Glu Ala Ile Ala Val Pro Ty - #r Met Ala Lys                          1250     - #           1255      - #          1260                 - - Phe Leu Ile Phe Ala Arg Arg Thr Phe Pro Al - #a Glu Gly Gln                              1265 - #               1270                                    - - Leu Arg Leu Phe Cys Met Thr Asp Asp Arg Gl - #u Asp Lys Thr              1275                1280 - #                1285                               - - Leu Glu Lys Gln Glu Arg Phe Ile Glu Ile Al - #a Lys Ser Lys                  1290             - #   1295              - #  1300                         - - Asp Val Glu Val Leu Ser Gly Arg His Gln Ph - #e Leu Glu Phe                      1305         - #       1310          - #      1315                     - - Ser Gly Asn Leu Leu Pro Ile Thr Lys Ser Gl - #y Asp Gln Leu                          1320     - #           1325      - #          1330                 - - Ser Leu Tyr Phe Leu Pro Phe Gln Glu Asn Ar - #g Leu Ala Phe                              1335 - #               1340                                    - - Met Val Lys Ile Arg Thr His Thr Asp Asn Gl - #u Thr Ala Ala              1345                1350 - #                1355                               - - Asp Gly Arg Ile Val Phe Met Lys Glu Pro Ly - #s Leu Arg Ala                  1360             - #   1365              - #  1370                         - - Glu Asn Leu Pro Pro Gln Thr Pro Val Cys Th - #r Leu Ala Ile                      1375         - #       1380          - #      1385                     - - Thr Leu Pro Glu Tyr Thr Gly Pro Glu Pro Me - #t Val Ser Lys                          1390     - #           1395      - #          1400                 - - Lys Leu Phe Tyr Ser Glu Ala Ser Leu Thr Gl - #u Lys Tyr Val                              1405 - #               1410                                    - - Gly Ala Phe His Glu Thr Ala Glu Pro Asp As - #n Leu Pro Leu              1415                1420 - #                1425                               - - Ala His Val Ala Leu Leu Ile Gly Ala Asp Tr - #p His Arg Leu                  1430             - #   1435              - #  1440                         - - Ala Arg Ala Leu Glu Val Pro Asp Ile Asp Il - #e Arg Gln Val                      1445         - #       1450          - #      1455                     - - Arg His Gln Leu Val Gly Leu Glu Ala Val Th - #r Ile Leu Arg                          1460     - #           1465      - #          1470                 - - Ile Trp Ile Phe Leu Lys Lys Glu Gln Ala Th - #r Pro Val Ala                              1475 - #               1480                                    - - Leu Arg Ser Ala Leu Gln Arg Ile Gly Arg As - #p Asp Val Val              1485                1490 - #                1495                               - - Arg Glu Met Asp Arg Ala Glu Lys Leu Asp Gl - #y Leu Glu Gly                  1500             - #   1505              - #  1510                         - - Thr Pro Val Ser His Ile Ser Gly Pro Ser Il - #e Thr Leu Ser                      1515         - #       1520          - #      1525                     - - Ser Thr Leu Leu Glu Val Ala Gly Asp Arg Ar - #g Arg His Ala                          1530     - #           1535      - #          1540                 - - Glu Val Thr Met Ala Gln Gln Arg Leu Ala Gl - #n Glu Pro Phe                              1545 - #               1550                                    - - Phe Gln Gln Val Gly Tyr Asn Gly Thr Pro Gl - #y Asp Pro Glu              1555                1560 - #                1565                               - - Glu Pro Lys Glu Gln Ser Phe His Glu Glu Gl - #u Glu Glu Val                  1570             - #   1575              - #  1580                         - - Ala Val Ser Glu Ile Arg Thr Val Val Arg Th - #r Glu Arg His                      1585         - #       1590          - #      1595                     - - Val His Asp Ser Glu Asn Gly Pro Ile Val Gl - #u Glu Arg Thr                          1600     - #           1605      - #          1610                 - - Ile Thr Thr Thr Tyr Glu Asp Asp Val Ala Va - #l Asn Glu Glu                              1615 - #               1620                                    - - Glu Ile Val Asp Lys Ile Val Pro Leu Asn Gl - #u Glu Glu Gln              1625                1630 - #                1635                               - - Glu Lys Trp Asp Arg Met Val Arg Glu Val Gl - #u Met Asn Phe                  1640             - #   1645              - #  1650                         - - Glu Gln Gln Glu Thr Ser Lys Glu Gly Thr Ph - #e Gly Cys Gln                      1655         - #       1660          - #      1665                     - - Thr Thr His Glu Lys Glu Lys Asp Asp Asp Gl - #y Gly Ser Leu                          1670     - #           1675      - #          1680                 - - Lys Thr Thr Met Lys Asp Ser His Val Arg Gl - #n Ile Phe Phe                              1685 - #               1690                                    - - Asp Gly Gly Glu Thr Ser Ala Asn Glu Thr Gl - #y Leu Ser Ser              1695                1700 - #                1705                               - - Gly Asp Ala Asp Thr Ile Met Thr Pro Thr Th - #r Lys Glu Asp                  1710             - #   1715              - #  1720                         - - Asn His Val Ile Asp Val Met Glu Glu Arg Ar - #g Thr Asp Glu                      1725         - #       1730          - #      1735                     - - Glu Ala Lys Gly Gln Ser Val His Glu                                                  1740     - #           1745                                        - -  - - (2) INFORMATION FOR SEQ ID NO:34:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  5503 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #34:                         - - TTTTTTTTTT TTTTTTTTTT TTTTACTGGA GCAAATTTAT CAAGAGTAGC  - #                  50                                                                         - - AGTTACAGAC TACAGCAAAA ACAAAAAGTG AATGGACGAT GGAAAACGCT  - #                 100                                                                         - - TTAACAATAT GGGAAGCCCA AACAGCATTC AAATTATTGC TTTGAAAAAT  - #                 150                                                                         - - TTCATTAAAT ATTAGCAACA TAGGCATGTG CGAGATTGCG ATTTAAATCA  - #                 200                                                                         - - ATTTGTGGAT CCAGATTATT CATGAACGCT TTGCCCTTTG GCCTCTTCAT  - #                 250                                                                         - - CAGTTCGCCT TTCCTCCATT ACGTCTATAA CATGATTATC CTCCTTTGTC  - #                 300                                                                         - - GTTGGAGTCA TAATAGTGTC TGCATCCCCG CTACTTAATC CTGTTTCATT  - #                 350                                                                         - - AGCGGATGTC TCACCTCCAT CGAAGAAAAT CTGCCTTACG TGACTATCTT  - #                 400                                                                         - - TCATTGTCGT CTTCAGACTG CCACCATCAT CATCTTTTTC TTTCTCATGT  - #                 450                                                                         - - GTTGTCTGAC AACCAAACGT TCCTTCTTTT GATGTTTCTT GTTGCTCAAA  - #                 500                                                                         - - ATTCATTTCC ACTTCTCGAA CCATTCGATC CCATTTTTCT TGCTCCTCTT  - #                 550                                                                         - - CGTTGAGAGG CACTATTTTG TCAACAATTT CTTCTTCGTT TACAGCAACA  - #                 600                                                                         - - TCATCCTCAT ACGTAGTTGT TATTGTACGC TCTTCCACAA TAGGACCATT  - #                 650                                                                         - - TTCCGAATCA TGCACATGTC GTTCAGTGCG CACAACTGTT CGAATTTCTG  - #                 700                                                                         - - AAACTGCAAC TTCCTCTTCC TCTTCGTGGA ATGACTGTTC TTTGGGTTCT  - #                 750                                                                         - - TCTGGATCTC CAGGTGTCCC ATTATACCCT ACTTGCTGAA AAAACGGTTC  - #                 800                                                                         - - TTGTGCCAAT CGCTGTTGCG CCATTGTTAC CTCGGCGTGA CGACGTCTGT  - #                 850                                                                         - - CGCCTGCTAC CTCTAGCAAA GTAGATGACA GAGTTATTGA GGGTCCAGAA  - #                 900                                                                         - - ATATGCGATA CAGGTGTTCC TTCTAAACCA TCTAGCTTTT CAGCTCGATC  - #                 950                                                                         - - CATTTCTCGT ACAACATCAT CACGTCCTAT TCGCTGCAAT GCTGATCGCA  - #                1000                                                                         - - AAGCAACGGG CGTAGCTTGT TCTTTCTTCA AAAATATCCA AATACGTAGA  - #                1050                                                                         - - ATAGTGACTG CTTCAAGACC AACTAGTTGA TGTCGAACTT GTCGTATATC  - #                1100                                                                         - - AATATCAGGT ACTTCAAGCG CTCGAGCTAA CCGATGCCAA TCAGCGCCAA  - #                1150                                                                         - - TTAATAGTGC AACATGTGCT AGTGGCAAGT TATCAGGTTC AGCAGTTTCA  - #                1200                                                                         - - TGGAAAGCTC CAACGTATTT CTCAGTCAAA GAAGCTTCCG AATAGAAGAG  - #                1250                                                                         - - TTTTTTGGAA ACCATCGGCT CCGGCCCAGT GTATTCCGGA AGAGTGATTG  - #                1300                                                                         - - CAAGAGTACA CACTGGCGTC TGCGGAGGTA AATTTTCGGC TCTCAATTTT  - #                1350                                                                         - - GGTTCTTTCA TAAATACTAT CCGGCCATCA GCTGCAGTTT CGTTGTCCGT  - #                1400                                                                         - - GTGAGTGCGT ATCTTTACCA TGAAAGCAAG ACGATTTTCT TGGAATGGTA  - #                1450                                                                         - - GAAAATAAAG AGAAAGTTGG TCACCACTCT TGGTTATTGG AAGAAGATTT  - #                1500                                                                         - - CCAGAAAATT CCAAAAACTG ATGTCGCCCA CTTAAGACTT CTACATCTTT  - #                1550                                                                         - - CGATTTCGCA ATTTCAATGA AACGTTCTTG TTTTTCCAGG GTTTTATCTT  - #                1600                                                                         - - CCCGATCATC AGTCATACAA AACAATCTCA ACTGTCCTTC GGCAGGAAAA  - #                1650                                                                         - - GTTCGTCGAG CAAAAATAAG AAATTTAGCC ATATAAGGAA CTGCAATTGC  - #                1700                                                                         - - TTCATTGTAA ACTTCTTGTG CCATTCGTGC CGCATCTCGC GGAGTTTGGC  - #                1750                                                                         - - AATCCATCAA CCAAAATCGA GCAGAAACCG TAGTTGTAAA TGAAACGTCC  - #                1800                                                                         - - TCACCAGTAA ATGTTAACTG GGTAGTTCCA GTAATATCTT CCCACTGTGC  - #                1850                                                                         - - AGGAGAAGAA CCTCCAGTTT TACTGCAGAG TAAACGCAGC GTCGGTGGTT  - #                1900                                                                         - - CCTGTCCTGG TTGGCCACTA TATTGTGTTA ACATTCCTTT ATTTGAGCTT  - #                1950                                                                         - - TGTGGCAATG GTATGCACAG CGTTATGGGC TTATGGAATT TGCGACGACG  - #                2000                                                                         - - CGGTTCAACA GTTACAATTG GAGAAACAGC GACTCTATTC CCATGTAAAC  - #                2050                                                                         - - GAGTGACTAT CTCTTGTGGA ACTGGCTGGG CTTGCACAGA TACTTTGATC  - #                2100                                                                         - - GTCTTAGTCA AGGAACCATC CGGAAATATG GCCTGCACAT GAGGAACAAC  - #                2150                                                                         - - TGAAGAGAGT ATTACACCAC CTTCTGGACC AACACAGTGC ACTTCTTGCC  - #                2200                                                                         - - GCACACGAGT AACGACCGCG AAATACATTG GGAAATCATT GGTCAGGATA  - #                2250                                                                         - - CGCGTAATCC GTGATGTATG CAAATCATCA AGTTGCGACA ACTCTTCTGC  - #                2300                                                                         - - ATCAAACGAT TCATTGAGCA CCTCTTGTAC AGCATCTTCT GTTGCTTCAA  - #                2350                                                                         - - GCTGATGCTC TTTCCAATGC TGCCCATCAT CAGAACGCAA AATGACAATC  - #                2400                                                                         - - TCTCTCTCTC GTCCACGAAG TGATGCAAAA TGTGGTACTT CCAATATAAC  - #                2450                                                                         - - AGGGCCTAAG AATTTTGCTC CATGTGGTGC CATTTCAAGT ATACGTGANG  - #                2500                                                                         - - CGAGCGCTTC ACCTTCACTT AATGGTGGTG GATGCGCTAA CTTGTCCTTT  - #                2550                                                                         - - CCAAGGTATC TGCATGTGAC CCGTGTAGGT TGCGGCGCTT TCCTCGGTGG  - #                2600                                                                         - - TATAATGATT CTGACACCGG AATGCCTACA ACCACGCATT GCTCCTCCAC  - #                2650                                                                         - - GTGCATCCAC CATAAACGAA ATTAAAAAAC TAGGTTGCAT GGTAGTTCTC  - #                2700                                                                         - - ATTATCGTAA CATTGTCAGG AAGCGATGCA TCTAAGGAAG GATCGGCCAT  - #                2750                                                                         - - CGCTGTAGTA ATTGGTTCAT GTTGTGCTTT ACGAATTAAG GCATCCAAAT  - #                2800                                                                         - - CGCCATCCGT ACCTTCCACT TCCGGACTTC GTGACAATGT CGGTTCTGTG  - #                2850                                                                         - - GCATGAATCA AATGTACACC AGTTGAATCG TGCAAACCTT TTGTGAGGCT  - #                2900                                                                         - - TTCTGAGAAA TCATGAGCAT GAGCATTGGC TGTGATCTGA TTATCTTCAC  - #                2950                                                                         - - CTTCATCTTC GGAATCGGAA AACATGGTTT CATTCATTGC TTCGGGATTC  - #                3000                                                                         - - TGAGGTTTAT ATCTTTCTTC AGTAACGGTT GTGGTCTCCG TTATCACAGT  - #                3050                                                                         - - AGTCTCGGTA ATTGTTTTAA GCGCTTCAAC CACGGATACA TACCCTAGAC  - #                3100                                                                         - - GTTCAGCAAT CGATAATGGA GTTTGTCCTG TCGATGTATG AACATTTGGA  - #                3150                                                                         - - CTTGCACCAT GTTCCAACAA GTAACGTACA ACACTGTTAT GCCCTTGCTG  - #                3200                                                                         - - AGCAGCTTGA TGCAGAGGAG TATAGGAAGC ACGAGTAATA ACTGAAACTC  - #                3250                                                                         - - GTGCGCCATG CTCAATCAAG AAACGGACCA TGTTTATTTG TCCAAAATGG  - #                3300                                                                         - - CAAGCAACAT GTAACGGCGT ATATCCTGCT TTCGTTTTGG GATCAATGGC  - #                3350                                                                         - - TGCGTTTTCT TTCACTAGTT CTTCTGCTAC GCTCACACGA TCCTCCTGTG  - #                3400                                                                         - - CACATAAATG CATTGGTGTC AAGCCATTCC TTGCCTGAGC TCCAACTTTT  - #                3450                                                                         - - GCTCCATTTT CAATTAATAA CGCAGCCATT TCGCGATGGC CCTCCTGGGC  - #                3500                                                                         - - GGCAAGATGA AGTGGTGTAA AGCCAGCTTT GCTTTCAGCA TTCGCATTTG  - #                3550                                                                         - - CCTTATAATG AAGGAGAGTG CTAGCAATAT CCATCTGATT CTTCTTCGCG  - #                3600                                                                         - - GCAATATGTA AAGGAGTGTA CCCATTCTTG GCAGCGGCAT GTGCAGAAGC  - #                3650                                                                         - - ACCATTTTCT AGAAGTAACA ATGCTACCTT GTCGTTATTG TAATGTGCCG  - #                3700                                                                         - - CTACATGCAG AGGTGTTACC TGATTCTTGC CTTCAATGTC AACCGGTGTT  - #                3750                                                                         - - CCTCGTTCTA GCAATGATTT CGCGACCGGC AAATTGCCAT ACTTAGCAGC  - #                3800                                                                         - - TAAATGCAAC GGCGTAAAAC CCTTTTTCGT GAGCAGTGTC TTGTCGGTTC  - #                3850                                                                         - - CATGATCCAT CAATATTGCT GCCACTTCCT CTTGCCCCTC CTTGGCAGCA  - #                3900                                                                         - - ATATGAAGAG GAGTATAAAG ATCTCTTGTG GCAGCATTTG GTGATGCATT  - #                3950                                                                         - - AGCCTGCAGC AACAAAATGA CGATGTCGGT ATTACCAAGA CGTGATGCAA  - #                4000                                                                         - - TGTGCAGTGG AGTTTGTAGT TCACGAGCAG CAGCATCCAC CTGTGCTCCA  - #                4050                                                                         - - TTACGCACCA AAACACGAAC AATGTCCGTT TGGTTTGCTC GTGCAGCTAA  - #                4100                                                                         - - ATGAAGAGGC GTTTCACCGC GTACTGTAGC CACATCTGCA TTAGCACCTT  - #                4150                                                                         - - GTTGTAGTAA ATAGATGACA ATGTTTATAG CACCCATAAA AGCAGCGACA  - #                4200                                                                         - - TGCAGCGGTG AGAGACCGGA TTCAGTAGTT GCTTCGATTG CAGCGTGGTA  - #                4250                                                                         - - TTTCAGTAGC AGTTCGACAA TTTTAATGCG ATTTTTTTTG CAAGCGATAT  - #                4300                                                                         - - GCAGCGGTGT GAAGCCATTG AGAGCTCGAG CATTCGGGTC AGCATTACGA  - #                4350                                                                         - - TCCAGCAAAA GTTTAGCGAC ACGGACATGT CCGCAATGAG CAGCCACATG  - #                4400                                                                         - - AAGAGGAGTG AGATAGTCAA CAGTAACATC ATCCACCTGT GCTGCCATAT  - #                4450                                                                         - - GTAAGGGAGC CAAACCATTT TTTGTCTTAG CACTGATTGG AGCTCCTTTT  - #                4500                                                                         - - TCAAGCAACA AATCAACAAC TTGATCATGA CCTGAACGAG AAGCACAGTG  - #                4550                                                                         - - TAATGGTGTT AGTAAATCAC GTGTGCGACA GTCAATTACG GCCCCATGAG  - #                4600                                                                         - - CCAACAATAA CGAAACCATG TTTGTACGAC CCCATTTTGT TGCAACGTGT  - #                4650                                                                         - - AACGGACTTA TGTTATGTCT CGCTTGGTAA TTCACATTGG CTCCCTTTTC  - #                4700                                                                         - - GAGTAGCAGT TGTGCTACGT TCTCATTTCC ATAGTGAGCG GCGATATGAA  - #                4750                                                                         - - GCGGAGTAAA GCCGCTTTTC GAAGTCACAT CCGAGTTATG CTCATTTTGA  - #                4800                                                                         - - AGTAATAGCG TAGCTGCTTT CGTATCATCT TTTTTAGCAG CAATATGCAG  - #                4850                                                                         - - TGCTGGCAAG CGCACTTTCC CGCGCGTGTC ATTTTCAAGC AAAACAGCGA  - #                4900                                                                         - - CCACACGATC GTGACCTTGT TGCAAGGCAA CTGCCAGTGG CGTAAAACCG  - #                4950                                                                         - - TCTTCTGTAC TTAAAGCTTG ATTGGCATTG TGGGCAAGAA GATAGCGTAC  - #                5000                                                                         - - AACAGATTCG TGATTTTCTT GTGCAGCCAT GTAAAGTGGT GTAAAACCGT  - #                5050                                                                         - - TTAGTGATTG TACGTTAACA TTAGCACCAT TTTCAACAAG TACTGTGACG  - #                5100                                                                         - - ATTAGTTCTT GTCCTGCCAA TGATGCTATA TGTAACGCTG TGTTACCCTT  - #                5150                                                                         - - TCTAGTGGCA GCATCAACAT CTGCTTTTCT TTTCAGAAGT TCGCGGACCA  - #                5200                                                                         - - CTTCATGATG ACCTTCTTTG GAGGCCAGAT GCAATGCATT AAGGCCATTC  - #                5250                                                                         - - GCATTGCATG TGTTGATATC GGTGCCCGAA CGAAGTAGTT CAAGTACACG  - #                5300                                                                         - - ATCCAAATTT CCAGCTCTTG CTGCTCGTAA AAAACTTGCA CTGCTCTCAC  - #                5350                                                                         - - CTTTGTTGGA ATGTTGACTG TTATCATCAG GAATTTGTTG TTGATGTTGT  - #                5400                                                                         - - GAATCTTTTG GTTCTGCGGG CCAGCCACTT CCCTCGACTA TAGGATTACT  - #                5450                                                                         - - CATCAATAGT TGAGTTATAT CAGTCAGCCG CCTCAAACTT GGGTAATTAA  - #                5500                                                                         - - ACC                  - #                  - #                  - #               5503                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:35:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  5235 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #35:                         - - ATGAGTAATC CTATAGTCGA GGGAAGTGGC TGGCCCGCAG AACCAAAAGA  - #                  50                                                                         - - TTCACAACAT CAACAACAAA TTCCTGATGA TAACAGTCAA CATTCCAACA  - #                 100                                                                         - - AAGGTGAGAG CAGTGCAAGT TTTTTACGAG CAGCAAGAGC TGGAAATTTG  - #                 150                                                                         - - GATCGTGTAC TTGAACTACT TCGTTCGGGC ACCGATATCA ACACATGCAA  - #                 200                                                                         - - TGCGAATGGC CTTAATGCAT TGCATCTGGC CTCCAAAGAA GGTCATCATG  - #                 250                                                                         - - AAGTGGTCCG CGAACTTCTG AAAAGAAAAG CAGATGTTGA TGCTGCCACT  - #                 300                                                                         - - AGAAAGGGTA ACACAGCGTT ACATATAGCA TCATTGGCAG GACAAGAACT  - #                 350                                                                         - - AATCGTCACA GTACTTGTTG AAAATGGTGC TAATGTTAAC GTACAATCAC  - #                 400                                                                         - - TAAACGGTTT TACACCACTT TACATGGCTG CACAAGAAAA TCACGAATCT  - #                 450                                                                         - - GTTGTACGCT ATCTTCTTGC CCACAATGCC AATCAAGCTT TAAGTACAGA  - #                 500                                                                         - - AGACGGTTTT ACGCCACTGG CAGTTGCCTT GCAACAAGGT CACGATCGTG  - #                 550                                                                         - - TGGTCGCTGT TTTGCTTGAA AATGACACGC GCGGGAAAGT GCGCTTGCCA  - #                 600                                                                         - - GCACTGCATA TTGCTGCTAA AAAAGATGAT ACGAAAGCAG CTACGCTATT  - #                 650                                                                         - - ACTTCAAAAT GAGCATAACT CGGATGTGAC TTCGAAAAGC GGCTTTACTC  - #                 700                                                                         - - CGCTTCATAT CGCCGCTCAC TATGGAAATG AGAACGTAGC ACAACTGCTA  - #                 750                                                                         - - CTCGAAAAGG GAGCCAATGT GAATTACCAA GCGAGACATA ACATAAGTCC  - #                 800                                                                         - - GTTACACGTT GCAACAAAAT GGGGTCGTAC AAACATGGTT TCGTTATTGT  - #                 850                                                                         - - TGGCTCATGG GGCCGTAATT GACTGTCGCA CACGTGATTT ACTAACACCA  - #                 900                                                                         - - TTACACTGTG CTTCTCGTTC AGGTCATGAT CAAGTTGTTG ATTTGTTGCT  - #                 950                                                                         - - TGAAAAAGGA GCTCCAATCA GTGCTAAGAC AAAAAATGGT TTGGCTCCCT  - #                1000                                                                         - - TACATATGGC AGCACAGGTG GATGATGTTA CTGTTGACTA TCTCACTCCT  - #                1050                                                                         - - CTTCATGTGG CTGCTCATTG CGGACATGTC CGTGTCGCTA AACTTTTGCT  - #                1100                                                                         - - GGATCGTAAT GCTGACCCGA ATGCTCGAGC TCTCAATGGC TTCACACCGC  - #                1150                                                                         - - TGCATATCGC TTGCAAAAAA AATCGCATTA AAATTGTCGA ACTGCTACTG  - #                1200                                                                         - - AAATACCACG CTGCAATCGA AGCAACTACT GAATCCGGTC TCTCACCGCT  - #                1250                                                                         - - GCATGTCGCT GCTTTTATGG GTGCTATAAA CATTGTCATC TATTTACTAC  - #                1300                                                                         - - AACAAGGTGC TAATGCAGAT GTGGCTACAG TACGCGGTGA AACGCCTCTT  - #                1350                                                                         - - CATTTAGCTG CACGAGCAAA CCAAACGGAC ATTGTTCGTG TTTTGGTGCG  - #                1400                                                                         - - TAATGGAGCA CAGGTGGATG CTGCTGCTCG TGAACTACAA ACTCCACTGC  - #                1450                                                                         - - ACATTGCATC ACGTCTTGGT AATACCGACA TCGTCATTTT GTTGCTGCAG  - #                1500                                                                         - - GCTAATGCAT CACCAAATGC TGCCACAAGA GATCTTTATA CTCCTCTTCA  - #                1550                                                                         - - TATTGCTGCC AAGGAGGGGC AAGAGGAAGT GGCAGCAATA TTGATGGATC  - #                1600                                                                         - - ATGGAACCGA CAAGACACTG CTCACGAAAA AGGGTTTTAC GCCGTTGCAT  - #                1650                                                                         - - TTAGCTGCTA AGTATGGCAA TTTGCCGGTC GCGAAATCAT TGCTAGAACG  - #                1700                                                                         - - AGGAACACCG GTTGACATTG AAGGCAAGAA TCAGGTAACA CCTCTGCATG  - #                1750                                                                         - - TAGCGGCACA TTACAATAAC GACAAGGTAG CATTGTTACT TCTAGAAAAT  - #                1800                                                                         - - GGTGCTTCTG CACATGCCGC TGCCAAGAAT GGGTACACTC CTTTACATAT  - #                1850                                                                         - - TGCCGCGAAG AAGAATCAGA TGGATATTGC TAGCACTCTC CTTCATTATA  - #                1900                                                                         - - AGGCAAATGC GAATGCTGAA AGCAAAGCTG GCTTTACACC ACTTCATCTT  - #                1950                                                                         - - GCCGCCCAGG AGGGCCATCG CGAAATGGCT GCGTTATTAA TTGAAAATGG  - #                2000                                                                         - - AGCAAAAGTT GGAGCTCAGG CAAGGAATGG CTTGACACCA ATGCATTTAT  - #                2050                                                                         - - GTGCACAGGA GGATCGTGTG AGCGTAGCAG AAGAACTAGT GAAAGAAAAC  - #                2100                                                                         - - GCAGCCATTG ATCCCAAAAC GAAAGCAGGA TATACGCCGT TACATGTTGC  - #                2150                                                                         - - TTGCCATTTT GGACAAATAA ACATGGTCCG TTTCTTGATT GAGCATGGCG  - #                2200                                                                         - - CACGAGTTTC AGTTATTACT CGTGCTTCCT ATACTCCTCT GCATCAAGCT  - #                2250                                                                         - - GCTCAGCAAG GGCATAACAG TGTTGTACGT TACTTGTTGG AACATGGTGC  - #                2300                                                                         - - AAGTCCAAAT GTTCATACAT CGACAGGACA AACTCCATTA TCGATTGCTG  - #                2350                                                                         - - AACGTCTAGG GTATGTATCC GTGGTTGAAG CGCTTAAAAC AATTACCGAG  - #                2400                                                                         - - ACTACTGTGA TAACGGAGAC CACAACCGTT ACTGAAGAAA GATATAAACC  - #                2450                                                                         - - TCAGAATCCC GAAGCAATGA ATGAAACCAT GTTTTCCGAT TCCGAAGATG  - #                2500                                                                         - - AAGGTGAAGA TAATCAGATC ACAGCCAATG CTCATGCTCA TGATTTCTCA  - #                2550                                                                         - - GAAAGCCTCA CAAAAGGTTT GCACGATTCA ACTGGTGTAC ATTTGATTCA  - #                2600                                                                         - - TGCCACAGAA CCGACATTGT CACGAAGTCC GGAAGTGGAA GGTACGGATG  - #                2650                                                                         - - GCGATTTGGA TGCCTTAATT CGTAAAGCAC AACATGAACC AATTACTACA  - #                2700                                                                         - - GCGATGGCCG ATCCTTCCTT AGATGCATCG CTTCCTGACA ATGTTACGAT  - #                2750                                                                         - - AATGAGAACT ACCATGCAAC CTAGTTTTTT AATTTCGTTT ATGGTGGATG  - #                2800                                                                         - - CACGTGGAGG AGCAATGCGT GGTTGTAGGC ATTCCGGTGT CAGAATCATT  - #                2850                                                                         - - ATACCACCGA GGAAAGCGCC GCAACCTACA CGGGTCACAT GCAGATACCT  - #                2900                                                                         - - TGGAAAGGAC AAGTTAGCGC ATCCACCACC ATTAAGTGAA GGTGAAGCGC  - #                2950                                                                         - - TCGCNTCACG TATACTTGAA ATGGCACCAC ATGGAGCAAA ATTCTTAGGC  - #                3000                                                                         - - CCTGTTATAT TGGAAGTACC ACATTTTGCA TCACTTCGTG GACGAGAGAG  - #                3050                                                                         - - AGAGATTGTC ATTTTGCGTT CTGATGATGG GCAGCATTGG AAAGAGCATC  - #                3100                                                                         - - AGCTTGAAGC AACAGAAGAT GCTGTACAAG AGGTGCTCAA TGAATCGTTT  - #                3150                                                                         - - GATGCAGAAG AGTTGTCGCA ACTTGATGAT TTGCATACAT CACGGATTAC  - #                3200                                                                         - - GCGTATCCTG ACCAATGATT TCCCAATGTA TTTCGCGGTC GTTACTCGTG  - #                3250                                                                         - - TGCGGCAAGA AGTGCACTGT GTTGGTCCAG AAGGTGGTGT AATACTCTCT  - #                3300                                                                         - - TCAGTTGTTC CTCATGTGCA GGCCATATTT CCGGATGGTT CCTTGACTAA  - #                3350                                                                         - - GACGATCAAA GTATCTGTGC AAGCCCAGCC AGTTCCACAA GAGATAGTCA  - #                3400                                                                         - - CTCGTTTACA TGGGAATAGA GTCGCTGTTT CTCCAATTGT AACTGTTGAA  - #                3450                                                                         - - CCGCGTCGTC GCAAATTCCA TAAGCCCATA ACGCTGTGCA TACCATTGCC  - #                3500                                                                         - - ACAAAGCTCA AATAAAGGAA TGTTAACACA ATATAGTGGC CAACCAGGAC  - #                3550                                                                         - - AGGAACCACC GACGCTGCGT TTACTCTGCA GTAAAACTGG AGGTTCTTCT  - #                3600                                                                         - - CCTGCACAGT GGGAAGATAT TACTGGAACT ACCCAGTTAA CATTTACTGG  - #                3650                                                                         - - TGAGGACGTT TCATTTACAA CTACGGTTTC TGCTCGATTT TGGTTGATGG  - #                3700                                                                         - - ATTGCCAAAC TCCGCGAGAT GCGGCACGAA TGGCACAAGA AGTTTACAAT  - #                3750                                                                         - - GAAGCAATTG CAGTTCCTTA TATGGCTAAA TTTCTTATTT TTGCTCGACG  - #                3800                                                                         - - AACTTTTCCT GCCGAAGGAC AGTTGAGATT GTTTTGTATG ACTGATGATC  - #                3850                                                                         - - GGGAAGATAA AACCCTGGAA AAACAAGAAC GTTTCATTGA AATTGCGAAA  - #                3900                                                                         - - TCGAAAGATG TAGAAGTCTT AAGTGGGCGA CATCAGTTTT TGGAATTTTC  - #                3950                                                                         - - TGGAAATCTT CTTCCAATAA CCAAGAGTGG TGACCAACTT TCTCTTTATT  - #                4000                                                                         - - TTCTACCATT CCAAGAAAAT CGTCTTGCTT TCATGGTAAA GATACGCACT  - #                4050                                                                         - - CACACGGACA ACGAAACTGC AGCTGATGGC CGGATAGTAT TTATGAAAGA  - #                4100                                                                         - - ACCAAAATTG AGAGCCGAAA ATTTACCTCC GCAGACGCCA GTGTGTACTC  - #                4150                                                                         - - TTGCAATCAC TCTTCCGGAA TACACTGGGC CGGAGCCGAT GGTTTCCAAA  - #                4200                                                                         - - AAACTCTTCT ATTCGGAAGC TTCTTTGACT GAGAAATACG TTGGAGCTTT  - #                4250                                                                         - - CCATGAAACT GCTGAACCTG ATAACTTGCC ACTAGCACAT GTTGCACTAT  - #                4300                                                                         - - TAATTGGCGC TGATTGGCAT CGGTTAGCTC GAGCGCTTGA AGTACCTGAT  - #                4350                                                                         - - ATTGATATAC GACAAGTTCG ACATCAACTA GTTGGTCTTG AAGCAGTCAC  - #                4400                                                                         - - TATTCTACGT ATTTGGATAT TTTTGAAGAA AGAACAAGCT ACGCCCGTTG  - #                4450                                                                         - - CTTTGCGATC AGCATTGCAG CGAATAGGAC GTGATGATGT TGTACGAGAA  - #                4500                                                                         - - ATGGATCGAG CTGAAAAGCT AGATGGTTTA GAAGGAACAC CTGTATCGCA  - #                4550                                                                         - - TATTTCTGGA CCCTCAATAA CTCTGTCATC TACTTTGCTA GAGGTAGCAG  - #                4600                                                                         - - GCGACAGACG TCGTCACGCC GAGGTAACAA TGGCGCAACA GCGATTGGCA  - #                4650                                                                         - - CAAGAACCGT TTTTTCAGCA AGTAGGGTAT AATGGGACAC CTGGAGATCC  - #                4700                                                                         - - AGAAGAACCC AAAGAACAGT CATTCCACGA AGAGGAAGAG GAAGTTGCAG  - #                4750                                                                         - - TTTCAGAAAT TCGAACAGTT GTGCGCACTG AACGACATGT GCATGATTCG  - #                4800                                                                         - - GAAAATGGTC CTATTGTGGA AGAGCGTACA ATAACAACTA CGTATGAGGA  - #                4850                                                                         - - TGATGTTGCT GTAAACGAAG AAGAAATTGT TGACAAAATA GTGCCTCTCA  - #                4900                                                                         - - ACGAAGAGGA GCAAGAAAAA TGGGATCGAA TGGTTCGAGA AGTGGAAATG  - #                4950                                                                         - - AATTTTGAGC AACAAGAAAC ATCAAAAGAA GGAACGTTTG GTTGTCAGAC  - #                5000                                                                         - - AACACATGAG AAAGAAAAAG ATGATGATGG TGGCAGTCTG AAGACGACAA  - #                5050                                                                         - - TGAAAGATAG TCACGTAAGG CAGATTTTCT TCGATGGAGG TGAGACATCC  - #                5100                                                                         - - GCTAATGAAA CAGGATTAAG TAGCGGGGAT GCAGACACTA TTATGACTCC  - #                5150                                                                         - - AACGACAAAG GAGGATAATC ATGTTATAGA CGTAATGGAG GAAAGGCGAA  - #                5200                                                                         - - CTGATGAAGA GGCCAAAGGG CAAAGCGTTC ATGAA       - #                  -     #     5235                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:36:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  5235 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #36:                         - - TTCATGAACG CTTTGCCCTT TGGCCTCTTC ATCAGTTCGC CTTTCCTCCA  - #                  50                                                                         - - TTACGTCTAT AACATGATTA TCCTCCTTTG TCGTTGGAGT CATAATAGTG  - #                 100                                                                         - - TCTGCATCCC CGCTACTTAA TCCTGTTTCA TTAGCGGATG TCTCACCTCC  - #                 150                                                                         - - ATCGAAGAAA ATCTGCCTTA CGTGACTATC TTTCATTGTC GTCTTCAGAC  - #                 200                                                                         - - TGCCACCATC ATCATCTTTT TCTTTCTCAT GTGTTGTCTG ACAACCAAAC  - #                 250                                                                         - - GTTCCTTCTT TTGATGTTTC TTGTTGCTCA AAATTCATTT CCACTTCTCG  - #                 300                                                                         - - AACCATTCGA TCCCATTTTT CTTGCTCCTC TTCGTTGAGA GGCACTATTT  - #                 350                                                                         - - TGTCAACAAT TTCTTCTTCG TTTACAGCAA CATCATCCTC ATACGTAGTT  - #                 400                                                                         - - GTTATTGTAC GCTCTTCCAC AATAGGACCA TTTTCCGAAT CATGCACATG  - #                 450                                                                         - - TCGTTCAGTG CGCACAACTG TTCGAATTTC TGAAACTGCA ACTTCCTCTT  - #                 500                                                                         - - CCTCTTCGTG GAATGACTGT TCTTTGGGTT CTTCTGGATC TCCAGGTGTC  - #                 550                                                                         - - CCATTATACC CTACTTGCTG AAAAAACGGT TCTTGTGCCA ATCGCTGTTG  - #                 600                                                                         - - CGCCATTGTT ACCTCGGCGT GACGACGTCT GTCGCCTGCT ACCTCTAGCA  - #                 650                                                                         - - AAGTAGATGA CAGAGTTATT GAGGGTCCAG AAATATGCGA TACAGGTGTT  - #                 700                                                                         - - CCTTCTAAAC CATCTAGCTT TTCAGCTCGA TCCATTTCTC GTACAACATC  - #                 750                                                                         - - ATCACGTCCT ATTCGCTGCA ATGCTGATCG CAAAGCAACG GGCGTAGCTT  - #                 800                                                                         - - GTTCTTTCTT CAAAAATATC CAAATACGTA GAATAGTGAC TGCTTCAAGA  - #                 850                                                                         - - CCAACTAGTT GATGTCGAAC TTGTCGTATA TCAATATCAG GTACTTCAAG  - #                 900                                                                         - - CGCTCGAGCT AACCGATGCC AATCAGCGCC AATTAATAGT GCAACATGTG  - #                 950                                                                         - - CTAGTGGCAA GTTATCAGGT TCAGCAGTTT CATGGAAAGC TCCAACGTAT  - #                1000                                                                         - - TTCTCAGTCA AAGAAGCTTC CGAATAGAAG AGTTTTTTGG AAACCATCGG  - #                1050                                                                         - - CTCCGGCCCA GTGTATTCCG GAAGAGTGAT TGCAAGAGTA CACACTGGCG  - #                1100                                                                         - - TCTGCGGAGG TAAATTTTCG GCTCTCAATT TTGGTTCTTT CATAAATACT  - #                1150                                                                         - - ATCCGGCCAT CAGCTGCAGT TTCGTTGTCC GTGTGAGTGC GTATCTTTAC  - #                1200                                                                         - - CATGAAAGCA AGACGATTTT CTTGGAATGG TAGAAAATAA AGAGAAAGTT  - #                1250                                                                         - - GGTCACCACT CTTGGTTATT GGAAGAAGAT TTCCAGAAAA TTCCAAAAAC  - #                1300                                                                         - - TGATGTCGCC CACTTAAGAC TTCTACATCT TTCGATTTCG CAATTTCAAT  - #                1350                                                                         - - GAAACGTTCT TGTTTTTCCA GGGTTTTATC TTCCCGATCA TCAGTCATAC  - #                1400                                                                         - - AAAACAATCT CAACTGTCCT TCGGCAGGAA AAGTTCGTCG AGCAAAAATA  - #                1450                                                                         - - AGAAATTTAG CCATATAAGG AACTGCAATT GCTTCATTGT AAACTTCTTG  - #                1500                                                                         - - TGCCATTCGT GCCGCATCTC GCGGAGTTTG GCAATCCATC AACCAAAATC  - #                1550                                                                         - - GAGCAGAAAC CGTAGTTGTA AATGAAACGT CCTCACCAGT AAATGTTAAC  - #                1600                                                                         - - TGGGTAGTTC CAGTAATATC TTCCCACTGT GCAGGAGAAG AACCTCCAGT  - #                1650                                                                         - - TTTACTGCAG AGTAAACGCA GCGTCGGTGG TTCCTGTCCT GGTTGGCCAC  - #                1700                                                                         - - TATATTGTGT TAACATTCCT TTATTTGAGC TTTGTGGCAA TGGTATGCAC  - #                1750                                                                         - - AGCGTTATGG GCTTATGGAA TTTGCGACGA CGCGGTTCAA CAGTTACAAT  - #                1800                                                                         - - TGGAGAAACA GCGACTCTAT TCCCATGTAA ACGAGTGACT ATCTCTTGTG  - #                1850                                                                         - - GAACTGGCTG GGCTTGCACA GATACTTTGA TCGTCTTAGT CAAGGAACCA  - #                1900                                                                         - - TCCGGAAATA TGGCCTGCAC ATGAGGAACA ACTGAAGAGA GTATTACACC  - #                1950                                                                         - - ACCTTCTGGA CCAACACAGT GCACTTCTTG CCGCACACGA GTAACGACCG  - #                2000                                                                         - - CGAAATACAT TGGGAAATCA TTGGTCAGGA TACGCGTAAT CCGTGATGTA  - #                2050                                                                         - - TGCAAATCAT CAAGTTGCGA CAACTCTTCT GCATCAAACG ATTCATTGAG  - #                2100                                                                         - - CACCTCTTGT ACAGCATCTT CTGTTGCTTC AAGCTGATGC TCTTTCCAAT  - #                2150                                                                         - - GCTGCCCATC ATCAGAACGC AAAATGACAA TCTCTCTCTC TCGTCCACGA  - #                2200                                                                         - - AGTGATGCAA AATGTGGTAC TTCCAATATA ACAGGGCCTA AGAATTTTGC  - #                2250                                                                         - - TCCATGTGGT GCCATTTCAA GTATACGTGA NGCGAGCGCT TCACCTTCAC  - #                2300                                                                         - - TTAATGGTGG TGGATGCGCT AACTTGTCCT TTCCAAGGTA TCTGCATGTG  - #                2350                                                                         - - ACCCGTGTAG GTTGCGGCGC TTTCCTCGGT GGTATAATGA TTCTGACACC  - #                2400                                                                         - - GGAATGCCTA CAACCACGCA TTGCTCCTCC ACGTGCATCC ACCATAAACG  - #                2450                                                                         - - AAATTAAAAA ACTAGGTTGC ATGGTAGTTC TCATTATCGT AACATTGTCA  - #                2500                                                                         - - GGAAGCGATG CATCTAAGGA AGGATCGGCC ATCGCTGTAG TAATTGGTTC  - #                2550                                                                         - - ATGTTGTGCT TTACGAATTA AGGCATCCAA ATCGCCATCC GTACCTTCCA  - #                2600                                                                         - - CTTCCGGACT TCGTGACAAT GTCGGTTCTG TGGCATGAAT CAAATGTACA  - #                2650                                                                         - - CCAGTTGAAT CGTGCAAACC TTTTGTGAGG CTTTCTGAGA AATCATGAGC  - #                2700                                                                         - - ATGAGCATTG GCTGTGATCT GATTATCTTC ACCTTCATCT TCGGAATCGG  - #                2750                                                                         - - AAAACATGGT TTCATTCATT GCTTCGGGAT TCTGAGGTTT ATATCTTTCT  - #                2800                                                                         - - TCAGTAACGG TTGTGGTCTC CGTTATCACA GTAGTCTCGG TAATTGTTTT  - #                2850                                                                         - - AAGCGCTTCA ACCACGGATA CATACCCTAG ACGTTCAGCA ATCGATAATG  - #                2900                                                                         - - GAGTTTGTCC TGTCGATGTA TGAACATTTG GACTTGCACC ATGTTCCAAC  - #                2950                                                                         - - AAGTAACGTA CAACACTGTT ATGCCCTTGC TGAGCAGCTT GATGCAGAGG  - #                3000                                                                         - - AGTATAGGAA GCACGAGTAA TAACTGAAAC TCGTGCGCCA TGCTCAATCA  - #                3050                                                                         - - AGAAACGGAC CATGTTTATT TGTCCAAAAT GGCAAGCAAC ATGTAACGGC  - #                3100                                                                         - - GTATATCCTG CTTTCGTTTT GGGATCAATG GCTGCGTTTT CTTTCACTAG  - #                3150                                                                         - - TTCTTCTGCT ACGCTCACAC GATCCTCCTG TGCACATAAA TGCATTGGTG  - #                3200                                                                         - - TCAAGCCATT CCTTGCCTGA GCTCCAACTT TTGCTCCATT TTCAATTAAT  - #                3250                                                                         - - AACGCAGCCA TTTCGCGATG GCCCTCCTGG GCGGCAAGAT GAAGTGGTGT  - #                3300                                                                         - - AAAGCCAGCT TTGCTTTCAG CATTCGCATT TGCCTTATAA TGAAGGAGAG  - #                3350                                                                         - - TGCTAGCAAT ATCCATCTGA TTCTTCTTCG CGGCAATATG TAAAGGAGTG  - #                3400                                                                         - - TACCCATTCT TGGCAGCGGC ATGTGCAGAA GCACCATTTT CTAGAAGTAA  - #                3450                                                                         - - CAATGCTACC TTGTCGTTAT TGTAATGTGC CGCTACATGC AGAGGTGTTA  - #                3500                                                                         - - CCTGATTCTT GCCTTCAATG TCAACCGGTG TTCCTCGTTC TAGCAATGAT  - #                3550                                                                         - - TTCGCGACCG GCAAATTGCC ATACTTAGCA GCTAAATGCA ACGGCGTAAA  - #                3600                                                                         - - ACCCTTTTTC GTGAGCAGTG TCTTGTCGGT TCCATGATCC ATCAATATTG  - #                3650                                                                         - - CTGCCACTTC CTCTTGCCCC TCCTTGGCAG CAATATGAAG AGGAGTATAA  - #                3700                                                                         - - AGATCTCTTG TGGCAGCATT TGGTGATGCA TTAGCCTGCA GCAACAAAAT  - #                3750                                                                         - - GACGATGTCG GTATTACCAA GACGTGATGC AATGTGCAGT GGAGTTTGTA  - #                3800                                                                         - - GTTCACGAGC AGCAGCATCC ACCTGTGCTC CATTACGCAC CAAAACACGA  - #                3850                                                                         - - ACAATGTCCG TTTGGTTTGC TCGTGCAGCT AAATGAAGAG GCGTTTCACC  - #                3900                                                                         - - GCGTACTGTA GCCACATCTG CATTAGCACC TTGTTGTAGT AAATAGATGA  - #                3950                                                                         - - CAATGTTTAT AGCACCCATA AAAGCAGCGA CATGCAGCGG TGAGAGACCG  - #                4000                                                                         - - GATTCAGTAG TTGCTTCGAT TGCAGCGTGG TATTTCAGTA GCAGTTCGAC  - #                4050                                                                         - - AATTTTAATG CGATTTTTTT TGCAAGCGAT ATGCAGCGGT GTGAAGCCAT  - #                4100                                                                         - - TGAGAGCTCG AGCATTCGGG TCAGCATTAC GATCCAGCAA AAGTTTAGCG  - #                4150                                                                         - - ACACGGACAT GTCCGCAATG AGCAGCCACA TGAAGAGGAG TGAGATAGTC  - #                4200                                                                         - - AACAGTAACA TCATCCACCT GTGCTGCCAT ATGTAAGGGA GCCAAACCAT  - #                4250                                                                         - - TTTTTGTCTT AGCACTGATT GGAGCTCCTT TTTCAAGCAA CAAATCAACA  - #                4300                                                                         - - ACTTGATCAT GACCTGAACG AGAAGCACAG TGTAATGGTG TTAGTAAATC  - #                4350                                                                         - - ACGTGTGCGA CAGTCAATTA CGGCCCCATG AGCCAACAAT AACGAAACCA  - #                4400                                                                         - - TGTTTGTACG ACCCCATTTT GTTGCAACGT GTAACGGACT TATGTTATGT  - #                4450                                                                         - - CTCGCTTGGT AATTCACATT GGCTCCCTTT TCGAGTAGCA GTTGTGCTAC  - #                4500                                                                         - - GTTCTCATTT CCATAGTGAG CGGCGATATG AAGCGGAGTA AAGCCGCTTT  - #                4550                                                                         - - TCGAAGTCAC ATCCGAGTTA TGCTCATTTT GAAGTAATAG CGTAGCTGCT  - #                4600                                                                         - - TTCGTATCAT CTTTTTTAGC AGCAATATGC AGTGCTGGCA AGCGCACTTT  - #                4650                                                                         - - CCCGCGCGTG TCATTTTCAA GCAAAACAGC GACCACACGA TCGTGACCTT  - #                4700                                                                         - - GTTGCAAGGC AACTGCCAGT GGCGTAAAAC CGTCTTCTGT ACTTAAAGCT  - #                4750                                                                         - - TGATTGGCAT TGTGGGCAAG AAGATAGCGT ACAACAGATT CGTGATTTTC  - #                4800                                                                         - - TTGTGCAGCC ATGTAAAGTG GTGTAAAACC GTTTAGTGAT TGTACGTTAA  - #                4850                                                                         - - CATTAGCACC ATTTTCAACA AGTACTGTGA CGATTAGTTC TTGTCCTGCC  - #                4900                                                                         - - AATGATGCTA TATGTAACGC TGTGTTACCC TTTCTAGTGG CAGCATCAAC  - #                4950                                                                         - - ATCTGCTTTT CTTTTCAGAA GTTCGCGGAC CACTTCATGA TGACCTTCTT  - #                5000                                                                         - - TGGAGGCCAG ATGCAATGCA TTAAGGCCAT TCGCATTGCA TGTGTTGATA  - #                5050                                                                         - - TCGGTGCCCG AACGAAGTAG TTCAAGTACA CGATCCAAAT TTCCAGCTCT  - #                5100                                                                         - - TGCTGCTCGT AAAAAACTTG CACTGCTCTC ACCTTTGTTG GAATGTTGAC  - #                5150                                                                         - - TGTTATCATC AGGAATTTGT TGTTGATGTT GTGAATCTTT TGGTTCTGCG  - #                5200                                                                         - - GGCCAGCCAC TTCCCTCGAC TATAGGATTA CTCAT       - #                  -     #     5235                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:37:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  908 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..906                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #37:                         - - GAT AAT GTT ACT GTT GAC TAT CTC ACT CCT CT - #T CAT GTG GCC                 - #  42                                                                    Asp Asn Val Thr Val Asp Tyr Leu Thr Pro Le - #u His Val Ala                   1               5   - #               10                                       - - GCC CAC TGC GGA CAT GTC CGT GTC GCT AAG CT - #T CTG CTG GAT                 - #  84                                                                    Ala His Cys Gly His Val Arg Val Ala Lys Le - #u Leu Leu Asp                   15                  - #20                  - #25                               - - CGT AAT GCC GAT TCA AAT GCT CGG GCT CTC AA - #T GGC TTC ACA                 - # 126                                                                    Arg Asn Ala Asp Ser Asn Ala Arg Ala Leu As - #n Gly Phe Thr                   30                  - #35                  - #40                               - - CCG TTG CAC ATA GCT TGC AAA AAA AAT CGC AT - #T AAG GTT GTC                 - # 168                                                                    Pro Leu His Ile Ala Cys Lys Lys Asn Arg Il - #e Lys Val Val                   45                  - #50                  - #55                               - - GAA CTG TTG CTG AAA TAT CAT GCT GCC ATC GA - #G GCA ACT ACA                 - # 210                                                                    Glu Leu Leu Leu Lys Tyr His Ala Ala Ile Gl - #u Ala Thr Thr                   60                  - #65                  - #70                               - - GAA TCC GGT CTG TCG CCG CTT CAC GTC GCT GC - #T TTC ATG GGT                 - # 252                                                                    Glu Ser Gly Leu Ser Pro Leu His Val Ala Al - #a Phe Met Gly                   75                  - #80                                                      - - GCT ATA AAC ATC GTT ATC TAC TTA CTG CAG CA - #G GGT GCT AAT                 - # 294                                                                    Ala Ile Asn Ile Val Ile Tyr Leu Leu Gln Gl - #n Gly Ala Asn                   85                  - #90                  - #95                               - - GCG AAT GTG GCT ACT GTA CGC GGT GAA ACA CC - #T CTT CAT TTA                 - # 336                                                                    Ala Asn Val Ala Thr Val Arg Gly Glu Thr Pr - #o Leu His Leu                   100                 1 - #05                 1 - #10                            - - GCT GCA CGA GCG AAC CAA ACC GAT ATT GTC CG - #T GTT TTG GTA                 - # 378                                                                    Ala Ala Arg Ala Asn Gln Thr Asp Ile Val Ar - #g Val Leu Val                   115                 1 - #20                 1 - #25                            - - CGT AAT GGA GCC CAG GTG GAT GCC GCG GCA CG - #T GAG CTA CAA                 - # 420                                                                    Arg Asn Gly Ala Gln Val Asp Ala Ala Ala Ar - #g Glu Leu Gln                   130                 1 - #35                 1 - #40                            - - ACA CCA TTA CAT ATT GCA TCA CGT CTT GGC AA - #T ACT GAT ATC                 - # 462                                                                    Thr Pro Leu His Ile Ala Ser Arg Leu Gly As - #n Thr Asp Ile                   145                 1 - #50                                                    - - GTT ATC TTG TTG CTG CAG GCA GAC GCA TCA CC - #A AAT GCT GCT                 - # 504                                                                    Val Ile Leu Leu Leu Gln Ala Asp Ala Ser Pr - #o Asn Ala Ala                   155                 1 - #60                 1 - #65                            - - ACA CGG GAT CTC TAC ACT CTT CTT CAT ATT GC - #T GCC AAA GAG                 - # 546                                                                    Thr Arg Asp Leu Tyr Thr Leu Leu His Ile Al - #a Ala Lys Glu                   170                 1 - #75                 1 - #80                            - - GGA CAA GAG GAG GTG GCA GCA ATA TTG ATA GA - #T CAT GGT TCC                 - # 588                                                                    Gly Gln Glu Glu Val Ala Ala Ile Leu Ile As - #p His Gly Ser                   185                 1 - #90                 1 - #95                            - - GAT AAG ACA TTG CTT ACC AAG AAA GGT TTT AC - #A CCG TTG CAT                 - # 630                                                                    Asp Lys Thr Leu Leu Thr Lys Lys Gly Phe Th - #r Pro Leu His                   200                 2 - #05                 2 - #10                            - - TTA GCT GCT AAA TAC GGC AAT TTA CCG GTA GC - #G AAA TTA TTG                 - # 672                                                                    Leu Ala Ala Lys Tyr Gly Asn Leu Pro Val Al - #a Lys Leu Leu                   215                 2 - #20                                                    - - CTG GAA CGA GGA ACT TTG GTT GAC ATT GAA GG - #C AAG AAC CAG                 - # 714                                                                    Leu Glu Arg Gly Thr Leu Val Asp Ile Glu Gl - #y Lys Asn Gln                   225                 2 - #30                 2 - #35                            - - GTG ACA CCT TTG CAT GTA GCA GCA CAT TAT AA - #T AAC GAC AAG                 - # 756                                                                    Val Thr Pro Leu His Val Ala Ala His Tyr As - #n Asn Asp Lys                   240                 2 - #45                 2 - #50                            - - GTA GCG CTG CTG CTT CTA GAA AGT GGT GCT TC - #C GCA CAT GCC                 - # 798                                                                    Val Ala Leu Leu Leu Leu Glu Ser Gly Ala Se - #r Ala His Ala                   255                 2 - #60                 2 - #65                            - - GTT GCC AAG AAT GGA TAT ACT CCT TTG CAT AT - #T GCT GCA AAG                 - # 840                                                                    Val Ala Lys Asn Gly Tyr Thr Pro Leu His Il - #e Ala Ala Lys                   270                 2 - #75                 2 - #80                            - - AAA AAT CAG ATG GAT ATT GCT AGC ACT CTT CT - #T CAT TAT AGG                 - # 882                                                                    Lys Asn Gln Met Asp Ile Ala Ser Thr Leu Le - #u His Tyr Arg                   285                 2 - #90                                                    - - GCA AAT GCG AAT GCT GAA AGC AAA GC    - #                  - #                 908                                                                     Ala Asn Ala Asn Ala Glu Ser Lys                                               295                 3 - #00                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:38:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  302 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #38:                         - - Asp Asn Val Thr Val Asp Tyr Leu Thr Pro Le - #u His Val Ala               1               5  - #                10                                      - - Ala His Cys Gly His Val Arg Val Ala Lys Le - #u Leu Leu Asp              15                  - #20                  - #25                               - - Arg Asn Ala Asp Ser Asn Ala Arg Ala Leu As - #n Gly Phe Thr                  30              - #    35              - #    40                           - - Pro Leu His Ile Ala Cys Lys Lys Asn Arg Il - #e Lys Val Val                      45          - #        50          - #        55                       - - Glu Leu Leu Leu Lys Tyr His Ala Ala Ile Gl - #u Ala Thr Thr                          60      - #            65      - #            70                   - - Glu Ser Gly Leu Ser Pro Leu His Val Ala Al - #a Phe Met Gly                              75  - #                80                                      - - Ala Ile Asn Ile Val Ile Tyr Leu Leu Gln Gl - #n Gly Ala Asn              85                  - #90                  - #95                               - - Ala Asn Val Ala Thr Val Arg Gly Glu Thr Pr - #o Leu His Leu                  100              - #   105              - #   110                          - - Ala Ala Arg Ala Asn Gln Thr Asp Ile Val Ar - #g Val Leu Val                      115          - #       120          - #       125                      - - Arg Asn Gly Ala Gln Val Asp Ala Ala Ala Ar - #g Glu Leu Gln                          130      - #           135      - #           140                  - - Thr Pro Leu His Ile Ala Ser Arg Leu Gly As - #n Thr Asp Ile                              145  - #               150                                     - - Val Ile Leu Leu Leu Gln Ala Asp Ala Ser Pr - #o Asn Ala Ala              155                 1 - #60                 1 - #65                            - - Thr Arg Asp Leu Tyr Thr Leu Leu His Ile Al - #a Ala Lys Glu                  170              - #   175              - #   180                          - - Gly Gln Glu Glu Val Ala Ala Ile Leu Ile As - #p His Gly Ser                      185          - #       190          - #       195                      - - Asp Lys Thr Leu Leu Thr Lys Lys Gly Phe Th - #r Pro Leu His                          200      - #           205      - #           210                  - - Leu Ala Ala Lys Tyr Gly Asn Leu Pro Val Al - #a Lys Leu Leu                              215  - #               220                                     - - Leu Glu Arg Gly Thr Leu Val Asp Ile Glu Gl - #y Lys Asn Gln              225                 2 - #30                 2 - #35                            - - Val Thr Pro Leu His Val Ala Ala His Tyr As - #n Asn Asp Lys                  240              - #   245              - #   250                          - - Val Ala Leu Leu Leu Leu Glu Ser Gly Ala Se - #r Ala His Ala                      255          - #       260          - #       265                      - - Val Ala Lys Asn Gly Tyr Thr Pro Leu His Il - #e Ala Ala Lys                          270      - #           275      - #           280                  - - Lys Asn Gln Met Asp Ile Ala Ser Thr Leu Le - #u His Tyr Arg                              285  - #               290                                     - - Ala Asn Ala Asn Ala Glu Ser Lys                                          295                 3 - #00                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:39:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  908 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #39:                         - - GCTTTGCTTT CAGCATTCGC ATTTGCCCTA TAATGAAGAA GAGTGCTAGC  - #                  50                                                                         - - AATATCCATC TGATTTTTCT TTGCAGCAAT ATGCAAAGGA GTATATCCAT  - #                 100                                                                         - - TCTTGGCAAC GGCATGTGCG GAAGCACCAC TTTCTAGAAG CAGCAGCGCT  - #                 150                                                                         - - ACCTTGTCGT TATTATAATG TGCTGCTACA TGCAAAGGTG TCACCTGGTT  - #                 200                                                                         - - CTTGCCTTCA ATGTCAACCA AAGTTCCTCG TTCCAGCAAT AATTTCGCTA  - #                 250                                                                         - - CCGGTAAATT GCCGTATTTA GCAGCTAAAT GCAACGGTGT AAAACCTTTC  - #                 300                                                                         - - TTGGTAAGCA ATGTCTTATC GGAACCATGA TCTATCAATA TTGCTGCCAC  - #                 350                                                                         - - CTCCTCTTGT CCCTCTTTGG CAGCAATATG AAGAAGAGTG TAGAGATCCC  - #                 400                                                                         - - GTGTAGCAGC ATTTGGTGAT GCGTCTGCCT GCAGCAACAA GATAACGATA  - #                 450                                                                         - - TCAGTATTGC CAAGACGTGA TGCAATATGT AATGGTGTTT GTAGCTCACG  - #                 500                                                                         - - TGCCGCGGCA TCCACCTGGG CTCCATTACG TACCAAAACA CGGACAATAT  - #                 550                                                                         - - CGGTTTGGTT CGCTCGTGCA GCTAAATGAA GAGGTGTTTC ACCGCGTACA  - #                 600                                                                         - - GTAGCCACAT TCGCATTAGC ACCCTGCTGC AGTAAGTAGA TAACGATGTT  - #                 650                                                                         - - TATAGCACCC ATGAAAGCAG CGACGTGAAG CGGCGACAGA CCGGATTCTG  - #                 700                                                                         - - TAGTTGCCTC GATGGCAGCA TGATATTTCA GCAACAGTTC GACAACCTTA  - #                 750                                                                         - - ATGCGATTTT TTTTGCAAGC TATGTGCAAC GGTGTGAAGC CATTGAGAGC  - #                 800                                                                         - - CCGAGCATTT GAATCGGCAT TACGATCCAG CAGAAGCTTA GCGACACGGA  - #                 850                                                                         - - CATGTCCGCA GTGGGCGGCC ACATGAAGAG GAGTGAGATA GTCAACAGTA  - #                 900                                                                         - - ACATTATC                - #                  - #                  -     #         908                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:40:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  906 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #40:                         - - GATAATGTTA CTGTTGACTA TCTCACTCCT CTTCATGTGG CCGCCCACTG  - #                  50                                                                         - - CGGACATGTC CGTGTCGCTA AGCTTCTGCT GGATCGTAAT GCCGATTCAA  - #                 100                                                                         - - ATGCTCGGGC TCTCAATGGC TTCACACCGT TGCACATAGC TTGCAAAAAA  - #                 150                                                                         - - AATCGCATTA AGGTTGTCGA ACTGTTGCTG AAATATCATG CTGCCATCGA  - #                 200                                                                         - - GGCAACTACA GAATCCGGTC TGTCGCCGCT TCACGTCGCT GCTTTCATGG  - #                 250                                                                         - - GTGCTATAAA CATCGTTATC TACTTACTGC AGCAGGGTGC TAATGCGAAT  - #                 300                                                                         - - GTGGCTACTG TACGCGGTGA AACACCTCTT CATTTAGCTG CACGAGCGAA  - #                 350                                                                         - - CCAAACCGAT ATTGTCCGTG TTTTGGTACG TAATGGAGCC CAGGTGGATG  - #                 400                                                                         - - CCGCGGCACG TGAGCTACAA ACACCATTAC ATATTGCATC ACGTCTTGGC  - #                 450                                                                         - - AATACTGATA TCGTTATCTT GTTGCTGCAG GCAGACGCAT CACCAAATGC  - #                 500                                                                         - - TGCTACACGG GATCTCTACA CTCTTCTTCA TATTGCTGCC AAAGAGGGAC  - #                 550                                                                         - - AAGAGGAGGT GGCAGCAATA TTGATAGATC ATGGTTCCGA TAAGACATTG  - #                 600                                                                         - - CTTACCAAGA AAGGTTTTAC ACCGTTGCAT TTAGCTGCTA AATACGGCAA  - #                 650                                                                         - - TTTACCGGTA GCGAAATTAT TGCTGGAACG AGGAACTTTG GTTGACATTG  - #                 700                                                                         - - AAGGCAAGAA CCAGGTGACA CCTTTGCATG TAGCAGCACA TTATAATAAC  - #                 750                                                                         - - GACAAGGTAG CGCTGCTGCT TCTAGAAAGT GGTGCTTCCG CACATGCCGT  - #                 800                                                                         - - TGCCAAGAAT GGATATACTC CTTTGCATAT TGCTGCAAAG AAAAATCAGA  - #                 850                                                                         - - TGGATATTGC TAGCACTCTT CTTCATTATA GGGCAAATGC GAATGCTGAA  - #                 900                                                                         - - AGCAAA                 - #                  - #                  -      #          906                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:41:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  906 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #41:                         - - TTTGCTTTCA GCATTCGCAT TTGCCCTATA ATGAAGAAGA GTGCTAGCAA  - #                  50                                                                        - - TATCCATCTG ATTTTTCTTT GCAGCAATAT GCAAAGGAGT ATATCCATTC  - #                 100                                                                         - - TTGGCAACGG CATGTGCGGA AGCACCACTT TCTAGAAGCA GCAGCGCTAC  - #                 150                                                                         - - CTTGTCGTTA TTATAATGTG CTGCTACATG CAAAGGTGTC ACCTGGTTCT  - #                 200                                                                         - - TGCCTTCAAT GTCAACCAAA GTTCCTCGTT CCAGCAATAA TTTCGCTACC  - #                 250                                                                         - - GGTAAATTGC CGTATTTAGC AGCTAAATGC AACGGTGTAA AACCTTTCTT  - #                 300                                                                         - - GGTAAGCAAT GTCTTATCGG AACCATGATC TATCAATATT GCTGCCACCT  - #                 350                                                                         - - CCTCTTGTCC CTCTTTGGCA GCAATATGAA GAAGAGTGTA GAGATCCCGT  - #                 400                                                                         - - GTAGCAGCAT TTGGTGATGC GTCTGCCTGC AGCAACAAGA TAACGATATC  - #                 450                                                                         - - AGTATTGCCA AGACGTGATG CAATATGTAA TGGTGTTTGT AGCTCACGTG  - #                 500                                                                         - - CCGCGGCATC CACCTGGGCT CCATTACGTA CCAAAACACG GACAATATCG  - #                 550                                                                         - - GTTTGGTTCG CTCGTGCAGC TAAATGAAGA GGTGTTTCAC CGCGTACAGT  - #                 600                                                                         - - AGCCACATTC GCATTAGCAC CCTGCTGCAG TAAGTAGATA ACGATGTTTA  - #                 650                                                                         - - TAGCACCCAT GAAAGCAGCG ACGTGAAGCG GCGACAGACC GGATTCTGTA  - #                 700                                                                         - - GTTGCCTCGA TGGCAGCATG ATATTTCAGC AACAGTTCGA CAACCTTAAT  - #                 750                                                                         - - GCGATTTTTT TTGCAAGCTA TGTGCAACGG TGTGAAGCCA TTGAGAGCCC  - #                 800                                                                         - - GAGCATTTGA ATCGGCATTA CGATCCAGCA GAAGCTTAGC GACACGGACA  - #                 850                                                                         - - TGTCCGCAGT GGGCGGCCAC ATGAAGAGGA GTGAGATAGT CAACAGTAAC  - #                 900                                                                         - - ATTATC                 - #                  - #                  -      #          906                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:42:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  23 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #42:                         - - CATCAATTTT TGGAATTTTC TGG           - #                  - #                    23                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:43:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  22 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #43:                         - - CGTTTACAGC AACATCATCC TC           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:44:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  22 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #44:                         - - GCACAACCAG TTCCGCAAGA AA           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:45:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #45:                         - - GGTTATTGGA AGAAGATTTC C           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:46:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  23 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  N =- # any nucleotide                                          (B) LOCATION:  9, 13                                                 - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #46:                         - - CAYCARGCNG CNCARCARGG NCA           - #                  - #                    23                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:47:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  23 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  N =- # any nucleotide                                          (B) LOCATION:  3, 13 - #, 16, 19                                     - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #47:                         - - GTNGAYGAYG TNACNGTNGA YTA           - #                  - #                    23                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:48:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  22 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #48:                         - - GGAATTTGCG ACGACGCGGT TC           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:49:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 17 nucleoti - #des                                                (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #49:                         - - CAGGAAACAG CTATGAC             - #                  - #                      - #   17                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:50:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  24 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #50:                         - - TGGAGTTTGT CCTGTCGATG TATG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:51:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  27 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #51:                         - - GCTTTGCTTT CAGCATTCGC ATTTGCC          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:52:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  22 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #52:                         - - GGTTTAATTA CCCAAGTTTG AG           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:53:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  27 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #53:                         - - GTGAGATAGT CAACAGTAAC ATCATCC          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:54:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  31 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #54:                         - - CGCGGATCCG GCACAACCAG TTCCGCAAGA A        - #                  - #              31                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:55:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  30 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #55:                         - - CCGGAATTCT TATTCATGAA CGCTTTGCCC         - #                  - #               30                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:56:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #56:                         - - CGCGGATTCG CGCGGTGCTA ATGCAGATGT GGC       - #                  - #            33                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:57:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  35 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #57:                         - - CCGGAATTCC GGTTACCCTA GACGTTCAGC AATCG       - #                  -     #       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:58:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  34 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #58:                         - - CGCGGATCCG CGCGCACGTG GAGGAGCAAT GCGT       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:59:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  36 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #59:                         - - CCGGAATTCC GGTTATTCGT TGTCCGTGTG AGTGCG      - #                       - #       36                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:60:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  37 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #60:                         - - CGCGGATCCG CGCCAACTAG TTGGTCTTGA AGCAGTC      - #                      - #      37                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:61:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #61:                         - - Glu Ser Ser Ala Ser Phe Leu Arg Ala Ala Ar - #g Ala Gly Asn               1               5  - #                10                                      - - Leu Asp Arg Val Leu Glu Leu Leu Arg Ser Gl - #y Thr Asp Ile              15                  - #20                  - #25                               - - Asn Thr Cys Asn Ala                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:62:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #62:                         - - Asn Gly Leu Asn Ala Leu His Leu Ala Ser Ly - #s Glu Gly His               1               5  - #                10                                      - - His Glu Val Val Arg Glu Leu Leu Lys Arg Ly - #s Ala Asp Val              15                  - #20                  - #25                               - - Asp Ala Ala Thr Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:63:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #63:                         - - Lys Gly Asn Thr Ala Leu His Ile Ala Ser Le - #u Ala Gly Gln               1               5  - #                10                                      - - Glu Leu Ile Val Thr Val Leu Val Glu Asn Gl - #y Ala Asn Val              15                  - #20                  - #25                               - - Asn Val Gln Ser Leu                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:64:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #64:                         - - Asn Gly Phe Thr Pro Leu Tyr Met Ala Ala Gl - #n Glu Asn His               1               5  - #                10                                      - - Glu Ser Val Val Arg Tyr Leu Leu Ala His As - #n Ala Asn Gln              15                  - #20                  - #25                               - - Ala Leu Ser Thr Glu                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:65:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  29 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #65:                         - - Asp Gly Phe Thr Pro Leu Ala Val Ala Leu Gl - #n Gln Gly His               1               5  - #                20                                      - - Asp Arg Val Val Ala Val Leu Leu Glu Asn As - #p Thr Arg Gly              15                  - #20                  - #25                               - - Lys                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:66:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #66:                         - - Val Arg Leu Pro Ala Leu His Ile Ala Ala Ly - #s Lys Asp Asp               1               5  - #                10                                      - - Thr Lys Ala Ala Thr Leu Leu Leu Gln Asn Gl - #u His Asn Ser              15                  - #20                  - #25                               - - Asp Val Thr Ser Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:67:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #67:                         - - Ser Gly Phe Thr Pro Leu His Ile Ala Ala Hi - #s Tyr Gly Asn               1               5  - #                10                                      - - Glu Asn Val Ala Gln Leu Leu Leu Glu Lys Gl - #y Ala Asn Val              15                  - #20                  - #25                               - - Asn Tyr Gln Ala Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:68:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #68:                         - - His Asn Ile Ser Pro Leu His Val Ala Thr Ly - #s Trp Gly Arg               1               5  - #                10                                      - - Thr Asn Met Val Ser Leu Leu Leu Ala His Gl - #y Ala Val Ile              15                  - #20                  - #25                               - - Asp Cys Arg Thr Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:69:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 33 amino - #acids                                                 (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #69:                         - - Asp Leu Leu Thr Pro Leu His Cys Ala Ser Ar - #g Ser Gly His               1               5  - #                10                                      - - Asp Gln Val Val Asp Leu Leu Leu Glu Lys Gl - #y Ala Pro Ile              15                  - #20                  - #25                               - - Ser Ala Lys Thr Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:70:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  17 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #70:                         - - Asn Gly Leu Ala Pro Leu His Met Ala Ala Gl - #n Val Asp Asp               1               5  - #                10                                      - - Val Thr Val                                                               15                                                                            - -  - - (2) INFORMATION FOR SEQ ID NO:71:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #71:                         - - Asp Tyr Leu Thr Pro Leu His Val Ala Ala Hi - #s Cys Gly His               1               5  - #                10                                      - - Val Arg Val Ala Lys Leu Leu Leu Asp Arg As - #n Ala Asp Pro              15                  - #20                  - #25                               - - Asn Ala Arg Ala Leu                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:72:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #72:                         - - Asn Gly Phe Thr Pro Leu His Ile Ala Cys Ly - #s Lys Asn Arg               1               5  - #                10                                      - - Ile Lys Ile Val Glu Leu Leu Leu Lys Tyr Hi - #s Ala Ala Ile              15                  - #20                  - #25                               - - Glu Ala Thr Thr Glu                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:73:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #73:                         - - Ser Gly Leu Ser Pro Leu His Val Ala Ala Ph - #e Met Gly Ala               1               5  - #                10                                      - - Ile Asn Ile Val Ile Tyr Leu Leu Gln Gln Gl - #y Ala Asn Ala              15                  - #20                  - #25                               - - Asp Val Ala Thr Val                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:74:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #74:                         - - Arg Gly Glu Thr Pro Leu His Leu Ala Ala Ar - #g Ala Asn Gln               1               5  - #                10                                      - - Thr Asp Ile Val Arg Val Leu Val Arg Asn Gl - #y Ala Gln Val              15                  - #20                  - #25                               - - Asp Ala Ala Ala Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:75:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #75:                         - - Glu Leu Gln Thr Pro Leu His Ile Ala Ser Ar - #g Leu Gly Asn               1               5  - #                10                                      - - Thr Asp Ile Val Ile Leu Leu Leu Gln Ala As - #n Ala Ser Pro              15                  - #20                  - #25                               - - Asn Ala Ala Thr Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:76:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #76:                         - - Asp Leu Tyr Thr Pro Leu His Ile Ala Ala Ly - #s Glu Gly Gln               1               5  - #                10                                      - - Glu Glu Val Ala Ala Ile Leu Met Asp His Gl - #y Thr Asp Lys              15                  - #20                  - #25                               - - Thr Leu Leu Thr Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:77:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #77:                         - - Lys Gly Phe Thr Pro Leu His Leu Ala Ala Ly - #s Tyr Gly Asn               1               5  - #                10                                      - - Leu Pro Val Ala Lys Ser Leu Leu Glu Arg Gl - #y Thr Pro Val              15                  - #20                  - #25                               - - Asp Ile Glu Gly Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:78:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #78:                         - - Asn Gln Val Thr Pro Leu His Val Ala Ala Hi - #s Tyr Asn Asn               1               5  - #                10                                      - - Asp Lys Val Ala Leu Leu Leu Leu Glu Asn Gl - #y Ala Ser Ala              15                  - #20                  - #25                               - - His Ala Ala Ala Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:79:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #79:                         - - Asn Gly Tyr Thr Pro Leu His Ile Ala Ala Ly - #s Lys Asn Gln               1               5  - #                10                                      - - Met Asp Ile Ala Ser Thr Leu Leu His Tyr Ly - #s Ala Asn Ala              15                  - #20                  - #25                               - - Asn Ala Glu Ser Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:80:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #80:                         - - Ala Gly Phe Thr Pro Leu His Leu Ala Ala Gl - #n Glu Gly His               1               5  - #                10                                      - - Arg Glu Met Ala Ala Leu Leu Ile Glu Asn Gl - #y Ala Lys Val              15                  - #20                  - #25                               - - Gly Ala Gln Ala Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:81:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #81:                         - - Asn Gly Leu Thr Pro Met His Leu Cys Ala Gl - #n Glu Asp Arg               1               5  - #                10                                      - - Val Ser Val Ala Glu Glu Leu Val Lys Glu As - #n Ala Ala Ile              15                  - #20                  - #25                               - - Asp Pro Lys Thr Lys                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:82:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #82:                         - - Ala Gly Tyr Thr Pro Leu His Val Ala Cys Hi - #s Phe Gly Gln               1               5  - #                10                                      - - Ile Asn Met Val Arg Phe Leu Ile Glu His Gl - #y Ala Arg Val              15                  - #20                  - #25                               - - Ser Val Ile Thr Arg                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:83:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #83:                         - - Ala Ser Tyr Thr Pro Leu His Gln Ala Ala Gl - #n Gln Gly His               1               5  - #                10                                      - - Asn Ser Val Val Arg Tyr Leu Leu Glu His Gl - #y Ala Ser Pro              15                  - #20                  - #25                               - - Asn Val His Thr Ser                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:84:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #84:                         - - Thr Gly Gln Thr Pro Leu Ser Ile Ala Glu Ar - #g Leu Gly Tyr               1               5  - #                10                                      - - Val Ser Val Val Glu Ala Leu Lys Thr Ile Th - #r Glu Thr Thr              15                  - #20                  - #25                               - - Val Ile Thr Glu Thr                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:85:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  33 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  protein                                          - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  Xaa =- # any amino acid                                        (B) LOCATION:  1, 3, - # 8, 11, 12, 15, 16,                                        17, 19, - #20, 23, 24, 27, 28,                                                30, 31, - #32, 33                                               - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  Xaa =- # Val or Ala                                            (B) LOCATION:  18                                                    - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  Xaa =- # Asn or Asp                                            (B) LOCATION:  29                                                    - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #85:                         - - Xaa Gly Xaa Thr Pro Leu His Xaa Ala Ala Xa - #a Xaa Gly His               1               5  - #                10                                      - - Xaa Xaa Xaa Xaa Xaa Xaa Leu Leu Xaa Xaa Gl - #y Ala Xaa Xaa              15                  - #20                  - #25                               - - Xaa Xaa Xaa Xaa Xaa                                                          30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:86:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  102 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..102                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #86:                         - - ATG AGT AAT CCT ATA GTC GAG GGA AGT GGC TG - #G CCC GCA GAA                 - #  42                                                                    Met Ser Asn Pro Ile Val Glu Gly Ser Gly Tr - #p Pro Ala Glu                    1               5  - #                10                                      - - CCA AAA GAT TCA CAA CAT CAA CAA CAA ATT CC - #T GAT GAT AAC                 - #  84                                                                    Pro Lys Asp Ser Gln His Gln Gln Gln Ile Pr - #o Asp Asp Asn                   15                  - #20                  - #25                               - - AGT CAA CAT TCC AAC AAA         - #                  - #                      - # 102                                                                  Ser Gln His Ser Asn Lys                                                           30                                                                         - - (2) INFORMATION FOR SEQ ID NO:87:                                         - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  102 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #87:                         - - TTTGTTGGAA TGTTGACTGT TATCATCAGG AATTTGTTGT TGATGTTGTG  - #                  50                                                                         - - AATCTTTTGG TTCTGCGGGC CAGCCACTTC CCTCGACTAT AGGATTACTC  - #                 100                                                                         - - AT                  - #                  - #                  - #                 102                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:88:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  201 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..201                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #88:                         - - GGT GAG AGC AGT GCA AGT TTT TTA CGA GCA GC - #A AGA GCT GGA                 - #  42                                                                    Gly Glu Ser Ser Ala Ser Phe Leu Arg Ala Al - #a Arg Ala Gly                   1               5   - #               10                                       - - AAT TTG GAT CGT GTA CTT GAA CTA CTT CGT TC - #G GGC ACC GAT                 - #  84                                                                    Asn Leu Asp Arg Val Leu Glu Leu Leu Arg Se - #r Gly Thr Asp                   15                  - #20                  - #25                               - - ATC AAC ACA TGC AAT GCG AAT GGC CTT AAT GC - #A TTG CAT CTG                 - # 126                                                                    Ile Asn Thr Cys Asn Ala Asn Gly Leu Asn Al - #a Leu His Leu                   30                  - #35                  - #40                               - - GCC TCC AAA GAA GGT CAT CAT GAA GTG GTC CG - #C GAA CTT CTG                 - # 168                                                                    Ala Ser Lys Glu Gly His His Glu Val Val Ar - #g Glu Leu Leu                   45                  - #50                  - #55                               - - AAA AGA AAA GCA GAT GTT GAT GCT GCC ACT AG - #A                  -      #        201                                                                    Lys Arg Lys Ala Asp Val Asp Ala Ala Thr Ar - #g                               60                  - #65                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:89:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  201 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #89:                         - - TCTAGTGGCA GCATCAACAT CTGCTTTTCT TTTCAGAAGT TCGCGGACCA  - #                  50                                                                        - - CTTCATGATG ACCTTCTTTG GAGGCCAGAT GCAATGCATT AAGGCCATTC  - #                 100                                                                         - - GCATTGCATG TGTTGATATC GGTGCCCGAA CGAAGTAGTT CAAGTACACG  - #                 150                                                                         - - ATCCAAATTT CCAGCTCTTG CTGCTCGTAA AAAACTTGCA CTGCTCTCAC  - #                 200                                                                         - - C                  - #                  - #                  - #                  201                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:90:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  187 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  2..187                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #90:                         - - T CCG TTA CAC GTT GCA ACA AAA TGG GGT CGT - #ACA AAC ATG                  - #   40                                                                     Pro Leu His Val Ala Thr Lys Trp Gly Arg Th - #r Asn Met                       1               5   - #               10                                       - - GTT TCG TTA TTG TTG GCT CAT GGG GCC GTA AT - #T GAC TGT CGC                 - #  82                                                                    Val Ser Leu Leu Leu Ala His Gly Ala Val Il - #e Asp Cys Arg                   15                  - #20                  - #25                               - - ACA CGT GAT TTA CTA ACA CCA TTA CAC TGT GC - #T TCT CGT TCA                 - # 124                                                                    Thr Arg Asp Leu Leu Thr Pro Leu His Cys Al - #a Ser Arg Ser                   30                  - #35                  - #40                               - - GGT CAT GAT CAA GTT GTT GAT TTG TTG CTT GA - #A AAA GGA GCT                 - # 166                                                                    Gly His Asp Gln Val Val Asp Leu Leu Leu Gl - #u Lys Gly Ala                   45                  - #50                  - #55                               - - CCA ATC AGT GCT AAG ACA AAA       - #                  - #                     187                                                                     Pro Ile Ser Ala Lys Thr Lys                                                   60                                                                             - -  - - (2) INFORMATION FOR SEQ ID NO:91:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  188 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #91:                         - - TTTTGTCTTA GCACTGATTG GAGCTCCTTT TTCAAGCAAC AAATCAACAA  - #                  50                                                                         - - CTTGATCATG ACCTGAACGA GAAGCACAGT GTAATGGTGT TAGTAAATCA  - #                 100                                                                         - - CGTGTGCGAC AGTCAATTAC GGCCCCATGA GCCAACAATA ACGAAACCAT  - #                 150                                                                         - - GTTTGTACGA CCCCATTTTG TTGCAACGTG TAACGGAC      - #                      - #    188                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:92:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  34 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..33                                                 - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #92:                         - - AAT GGT TTG GCT CCC TTA CAT ATG GCA GCA CA - #G G                 -     #        34                                                                    Asn Gly Leu Ala Pro Leu His Met Ala Ala Gl - #n                                1               5  - #                10                                      - -  - - (2) INFORMATION FOR SEQ ID NO:93:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  34 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #93:                         - - CCTGTGCTGC CATATGTAAG GGAGCCAAAC CATT       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:94:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  150 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..150                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #94:                         - - GTG GAT GCT GCT GCT CGT GAA CTA CAA ACT CC - #A CTG CAC ATT                 - #  42                                                                   Val Asp Ala Ala Ala Arg Glu Leu Gln Thr Pr - #o Leu His Ile                   1               5   - #               10                                       - - GCA TCA CGT CTT GGT AAT ACC GAC ATC GTC AT - #T TTG TTG CTG                 - #  84                                                                    Ala Ser Arg Leu Gly Asn Thr Asp Ile Val Il - #e Leu Leu Leu                   15                  - #20                  - #25                               - - CAG GCT AAT GCA TCA CCA AAT GCT GCC ACA AG - #A GAT CTT TAT                 - # 126                                                                    Gln Ala Asn Ala Ser Pro Asn Ala Ala Thr Ar - #g Asp Leu Tyr                   30                  - #35                  - #40                               - - ACT CCT CTT CAT ATT GCT GCC AAG     - #                  - #                   150                                                                     Thr Pro Leu His Ile Ala Ala Lys                                               45                  - #50                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:95:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  150 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #95:                         - - CTTGGCAGCA ATATGAAGAG GAGTATAAAG ATCTCTTGTG GCAGCATTTG  - #                  50                                                                         - - GTGATGCATT AGCCTGCAGC AACAAAATGA CGATGTCGGT ATTACCAAGA  - #                 100                                                                         - - CGTGATGCAA TGTGCAGTGG AGTTTGTAGT TCACGAGCAG CAGCATCCAC  - #                 150                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:96:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  161 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  3..161                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #96:                         - - GA CAA ATA AAC ATG GTC CGT TTC TTG ATT GAG - # CAT GGC GCA                 - #   41                                                                    Gln Ile Asn Met Val Arg Phe Leu Ile Glu Hi - #s Gly Ala                       1               5   - #               10                                       - - CGA GTT TCA GTT ATT ACT CGT GCT TCC TAT AC - #T CCT CTG CAT                 - #  83                                                                    Arg Val Ser Val Ile Thr Arg Ala Ser Tyr Th - #r Pro Leu His                   15                  - #20                  - #25                               - - CAA GCT GCT CAG CAA GGG CAT AAC AGT GTT GT - #A CGT TAC TTG                 - # 125                                                                    Gln Ala Ala Gln Gln Gly His Asn Ser Val Va - #l Arg Tyr Leu                   30                  - #35                  - #40                               - - TTG GAA CAT GGT GCA AGT CCA AAT GTT CAT AC - #A TCG                     - #      161                                                                    Leu Glu His Gly Ala Ser Pro Asn Val His Th - #r Ser                           45                  - #50                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:97:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  161 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #97:                         - - CGATGTATGA ACATTTGGAC TTGCACCATG TTCCAACAAG TAACGTACAA  - #                  50                                                                        - - CACTGTTATG CCCTTGCTGA GCAGCTTGAT GCAGAGGAGT ATAGGAAGCA  - #                 100                                                                         - - CGAGTAATAA CTGAAACTCG TGCGCCATGC TCAATCAAGA AACGGACCAT  - #                 150                                                                         - - GTTTATTTGT C               - #                  - #                      - #      161                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:98:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  133 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  2..133                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #98:                         - - T TTT TTA ATT TCG TTT ATG GTG GAT GCA CGT - #GGA GGA GCA ATG                - # 43                                                                     Phe Leu Ile Ser Phe Met Val Asp Ala Arg Gl - #y Gly Ala Met                   1               5   - #               10                                       - - CGT GGT TGT AGG CAT TCC GGT GTC AGA ATC AT - #T ATA CCA CCG                 - #  85                                                                    Arg Gly Cys Arg His Ser Gly Val Arg Ile Il - #e Ile Pro Pro                   15                  - #20                  - #25                               - - AGG AAA GCG CCG CAA CCT ACA CGG GTC ACA TG - #C AGA TAC CTT                 - # 127                                                                    Arg Lys Ala Pro Gln Pro Thr Arg Val Thr Cy - #s Arg Tyr Leu                   30                  - #35                  - #40                               - - GGA AAG                - #                  - #                  -      #          133                                                                  Gly Lys                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:99:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  133 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #99:                         - - CTTTCCAAGG TATCTGCATG TGACCCGTGT AGGTTGCGGC GCTTTCCTCG  - #                  50                                                                        - - GTGGTATAAT GATTCTGACA CCGGAATGCC TACAACCACG CATTGCTCCT  - #                 100                                                                         - - CCACGTGCAT CCACCATAAA CGAAATTAAA AAA       - #                  - #            133                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:100:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  179 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  3..179                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #100:                        - - CC GTT GCT TTG CGA TCA GCA TTG CAG CGA ATA - # GGA CGT GAT                 - #   41                                                                    Val Ala Leu Arg Ser Ala Leu Gln Arg Ile Gl - #y Arg Asp                       1               5   - #               10                                       - - GAT GTT GTA CGA GAA ATG GAT CGA GCT GAA AA - #G CTA GAT GGT                 - #  83                                                                    Asp Val Val Arg Glu Met Asp Arg Ala Glu Ly - #s Leu Asp Gly                   15                  - #20                  - #25                               - - TTA GAA GGA ACA CCT GTA TCG CAT ATT TCT GG - #A CCC TCA ATA                 - # 125                                                                    Leu Glu Gly Thr Pro Val Ser His Ile Ser Gl - #y Pro Ser Ile                   30                  - #35                  - #40                               - - ACT CTG TCA TCT ACT TTG CTA GAG GTA GCA GG - #C GAC AGA CGT                 - # 167                                                                    Thr Leu Ser Ser Thr Leu Leu Glu Val Ala Gl - #y Asp Arg Arg                   45                  - #50                  - #55                               - - CGT CAC GCC GAG            - #                  - #                      - #      179                                                                  Arg His Ala Glu                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:101:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  179 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #101:                        - - CTCGGCGTGA CGACGTCTGT CGCCTGCTAC CTCTAGCAAA GTAGATGACA  - #                  50                                                                         - - GAGTTATTGA GGGTCCAGAA ATATGCGATA CAGGTGTTCC TTCTAAACCA  - #                 100                                                                         - - TCTAGCTTTT CAGCTCGATC CATTTCTCGT ACAACATCAT CACGTCCTAT  - #                 150                                                                         - - TCGCTGCAAT GCTGATCGCA AAGCAACGG         - #                  - #               179                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:102:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  184 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..183                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #102:                        - - GTA ACA ATG GCG CAA CAG CGA TTG GCA CAA GA - #A CCG TTT TTT                 - #  42                                                                    Val Thr Met Ala Gln Gln Arg Leu Ala Gln Gl - #u Pro Phe Phe                   1               5   - #               10                                       - - CAG CAA GTA GGG TAT AAT GGG ACA CCT GGA GA - #T CCA GAA GAA                 - #  84                                                                    Gln Gln Val Gly Tyr Asn Gly Thr Pro Gly As - #p Pro Glu Glu                   15                  - #20                  - #25                               - - CCC AAA GAA CAG TCA TTC CAC GAA GAG GAA GA - #G GAA GTT GCA                 - # 126                                                                    Pro Lys Glu Gln Ser Phe His Glu Glu Glu Gl - #u Glu Val Ala                   30                  - #35                  - #40                               - - GTT TCA GAA ATT CGA ACA GTT GTG CGC ACT GA - #A CGA CAT GTG                 - # 168                                                                    Val Ser Glu Ile Arg Thr Val Val Arg Thr Gl - #u Arg His Val                   45                  - #50                  - #55                               - - CAT GAT TCG GAA AAT G         - #                  - #                      - #   184                                                                  His Asp Ser Glu Asn                                                           60                                                                             - -  - - (2) INFORMATION FOR SEQ ID NO:103:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  184 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #103:                        - - CATTTTCCGA ATCATGCACA TGTCGTTCAG TGCGCACAAC TGTTCGAATT  - #                  50                                                                         - - TCTGAAACTG CAACTTCCTC TTCCTCTTCG TGGAATGACT GTTCTTTGGG  - #                 100                                                                         - - TTCTTCTGGA TCTCCAGGTG TCCCATTATA CCCTACTTGC TGAAAAAACG  - #                 150                                                                         - - GTTCTTGTGC CAATCGCTGT TGCGCCATTG TTAC       - #                  -      #       184                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:104:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  158 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  3..158                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #104:                        - - GT CCT ATT GTG GAA GAG CGT ACA ATA ACA ACT - # ACG TAT GAG                 - #   41                                                                   Pro Ile Val Glu Glu Arg Thr Ile Thr Thr Th - #r Tyr Glu                       1               5   - #               10                                       - - GAT GAT GTT GCT GTA AAC GAA GAA GAA ATT GT - #T GAC AAA ATA                 - #  83                                                                    Asp Asp Val Ala Val Asn Glu Glu Glu Ile Va - #l Asp Lys Ile                   15                  - #20                  - #25                               - - GTG CCT CTC AAC GAA GAG GAG CAA GAA AAA TG - #G GAT CGA ATG                 - # 125                                                                    Val Pro Leu Asn Glu Glu Glu Gln Glu Lys Tr - #p Asp Arg Met                   30                  - #35                  - #40                               - - GTT CGA GAA GTG GAA ATG AAT TTT GAG CAA CA - #A                  -      #        158                                                                    Val Arg Glu Val Glu Met Asn Phe Glu Gln Gl - #n                               45                  - #50                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:105:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  158 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #105:                        - - TTGTTGCTCA AAATTCATTT CCACTTCTCG AACCATTCGA TCCCATTTTT  - #                  50                                                                        - - CTTGCTCCTC TTCGTTGAGA GGCACTATTT TGTCAACAAT TTCTTCTTCG  - #                 100                                                                         - - TTTACAGCAA CATCATCCTC ATACGTAGTT GTTATTGTAC GCTCTTCCAC  - #                 150                                                                         - - AATAGGAC                - #                  - #                  -     #         158                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:106:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  59 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  3..59                                                 - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #106:                        - - AC GTA ATG GAG GAA AGG CGA ACT GAT GAA GAG - # GCC AAA GGG                 - #   41                                                                    Val Met Glu Glu Arg Arg Thr Asp Glu Glu Al - #a Lys Gly                       1               5   - #               10                                       - - CAA AGC GTT CAT GAA TAA         - #                  - #                      - #  59                                                                  Gln Ser Val His Glu                                                           15                                                                             - -  - - (2) INFORMATION FOR SEQ ID NO:107:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  59 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #107:                        - - TTATTCATGA ACGCTTTGCC CTTTGGCCTC TTCATCAGTT CGCCTTTCCT  - #                  50                                                                         - - CCATTACGT                - #                  - #                       - #         59                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:108:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  92 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #108:                        - - GTATTTTCTT TATAAATGTA TATTATCGAA GGAAATAGCT GCATAAATGT  - #                  50                                                                        - - TAAGCCTTTT TATTGTAAGG AGGAACTAAA ATAATTTCGC AG    - #                      - #  92                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:109:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  92 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #109:                        - - CTGCGAAATT ATTTTAGTTC CTCCTTACAA TAAAAAGGCT TAACATTTAT  - #                  50                                                                         - - GCAGCTATTT CCTTCGATAA TATACATTTA TAAAGAAAAT AC    - #                      - #  92                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:110:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  118 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #110:                        - - GTCTTATTTG TGAATCCTTT TGTCCTTTTC TTTCTGTTGT TAATAGTTCG  - #                  50                                                                         - - CTTTTTCGAT TTTCACTTTT GTTGCATTGT TTATATAATC TTGCTGTTGA  - #                 100                                                                         - - TAATAATATT GTTTTCAG             - #                  - #                      - # 118                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:111:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  118 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #111:                        - - CTGAAAACAA TATTATTATC AACAGCAAGA TTATATAAAC AATGCAACAA  - #                  50                                                                         - - AAGTGAAAAT CGAAAAAGCG AACTATTAAC AACAGAAAGA AAAGGACAAA  - #                 100                                                                         - - AGGATTCACA AATAAGAC             - #                  - #                      - # 118                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:112:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  248 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #112:                        - - GTATGTAAAT GTATATGCTG GAAATATTAA AATGATTGAT TTAAAAAGGC  - #                  50                                                                         - - CATTGTAAAA ATACGATGAA GTAACTGCGT CCATAAATGG ATAACGATCT  - #                 100                                                                         - - TGAGAGTCAT CTGCCTGAAT TTTTTTAGAA TTCCAACACA AAGGTTTAAG  - #                 150                                                                         - - GCACTTGTTA AATAAATCTA GATAAGCATT TCAAAATTAT GCGTTAGATG  - #                 200                                                                         - - AGTATTCTAT CAATAACAGC TATTAATAAA ATTTTTTTTT TCCTTCAG  - #                   248                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:113:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  248 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #113:                        - - CTGAAGGAAA AAAAAAATTT TATTAATAGC TGTTATTGAT AGAATACTCA  - #                  50                                                                         - - TCTAACGCAT AATTTTGAAA TGCTTATCTA GATTTATTTA ACAAGTGCCT  - #                 100                                                                         - - TAAACCTTTG TGTTGGAATT CTAAAAAAAT TCAGGCAGAT GACTCTCAAG  - #                 150                                                                         - - ATCGTTATCC ATTTATGGAC GCAGTTACTT CATCGTATTT TTACAATGGC  - #                 200                                                                         - - CTTTTTAAAT CAATCATTTT AATATTTCCA GCATATACAT TTACATAC  - #                   248                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:114:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  94 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #114:                        - - GTAAGCAGTA TAGTTTTGGG ATTCTATTTC TGTTGTTGCC TCCTTTATAG  - #                  50                                                                         - - TTTTCAGAGA ATTTCATTGG ATAATCAAAT ATAAAACATT GCAG   - #                      - # 94                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:115:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  94 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #115:                        - - CTGCAATGTT TTATATTTGA TTATCCAATG AAATTCTCTG AAAACTATAA  - #                  50                                                                         - - AGGAGGCAAC AACAGAAATA GAATCCCAAA ACTATACTGC TTAC   - #                      - # 94                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:116:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  48 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #116:                        - - GTGATCATGT GGACAGTGCG CGAATTCTCT TGTATCATAG AGCTCCAG  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:117:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  48 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #117:                        - - CTGGAGCTCT ATGATACAAG AGAATTCGCG CACTGTCCAC ATGATCAC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:118:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  200 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #118:                        - - GTTAGTCGAT GTTGCATGCT TAAATACTAT CATCATTGAA AACTATTTTT  - #                  50                                                                         - - GCGGGAACCG GTATTTTATT CTTATTTCAG AGCATTGTTT AGTTTCGAAA  - #                 100                                                                         - - AGAAAGAAGA ATGCCATTCA TTCTATATGA AAGTGTATAG TATTGAAGCT  - #                 150                                                                         - - CCATTGCTAC AGTCATATTG AAGATTTCAT TATGTGATAT GTTTATAAAG  - #                 200                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:119:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  200 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #119:                        - - CTTTATAAAC ATATCACATA ATGAAATCTT CAATATGACT GTAGCAATGG  - #                  50                                                                         - - AGCTTCAATA CTATACACTT TCATATAGAA TGAATGGCAT TCTTCTTTCT  - #                 100                                                                         - - TTTCGAAACT AAACAATGCT CTGAAATAAG AATAAAATAC CGGTTCCCGC  - #                 150                                                                         - - AAAAATAGTT TTCAATGATG ATAGTATTTA AGCATGCAAC ATCGACTAAC  - #                 200                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:120:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  82 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #120:                        - - GTAAGCTTAG TGGAAAAAAG AAATATTTGC CTTTTTTAAT TAATTTAGAG  - #                  50                                                                         - - TGCATAAGTT ATTCAATTTC CAAATATTAT AG       - #                  - #              82                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:121:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  82 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #121:                        - - CTATAATATT TGGAAATTGA ATAACTTATG CACTCTAAAT TAATTAAAAA  - #                  50                                                                         - - AGGCAAATAT TTCTTTTTTC CACTAAGCTT AC       - #                  - #              82                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:122:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  213 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #122:                        - - GTGATCACTG ATATGATATT GGCGTTAAAT ATCTCTGTGT TCTTCGCAAT  - #                  50                                                                         - - AAATTAACTT GCCTTTTTAA GTCCGACCAG AAGACTTCCA GATACTAAAT  - #                 100                                                                         - - TATTTATAAT ATATTTTTAG ATTAATTCTT GCTCTTATCT TTCATTGTAA  - #                 150                                                                         - - ATATATTCAG TATGTTCAGA AAGATATTGA TATACGAATA TCAGTGATCA  - #                 200                                                                         - - TTGATTATTT TAG              - #                  - #                      - #     213                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:123:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  213 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #123:                        - - CTAAAATAAT CAATGATCAC TGATATTCGT ATATCAATAT CTTTCTGAAC  - #                  50                                                                         - - ATACTGAATA TATTTACAAT GAAAGATAAG AGCAAGAATT AATCTAAAAA  - #                 100                                                                         - - TATATTATAA ATAATTTAGT ATCTGGAAGT CTTCTGGTCG GACTTAAAAA  - #                 150                                                                         - - GGCAAGTTAA TTTATTGCGA AGAACACAGA GATATTTAAC GCCAATATCA  - #                 200                                                                         - - TATCAGTGAT CAC              - #                  - #                      - #     213                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:124:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  76 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #124:                        - - GTTCGATTTC TCCTCTTATG GAATTTTGTT GCTGTTCTTC TGTGTCATAC  - #                  50                                                                         - - TAATTATAAT ATTGAGAACG TTGCAG          - #                  - #                  76                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:125:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  76 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #125:                        - - CTGCAACGTT CTCAATATTA TAATTAGTAT GACACAGAAG AACAGCAACA  - #                  50                                                                         - - AAATTCCATA AGAGGAGAAA TCGAAC          - #                  - #                  76                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:126:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  231 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #126:                        - - GTAATAATTG ATTAATTTGG GAAAAAAAGT AACGTGTTAT CTTCGAAATT  - #                  50                                                                         - - ATGAAAAATT TATGTAGGAA GGCTTTTGAG TAATAGAACC ATTAAGCTTG  - #                 100                                                                         - - GCATTTAAGA GAAAAACAAC CTGACTGCTG CAATGAAGAG CTTTGTAAGA  - #                 150                                                                         - - AAAAGAAAAG TGTATGTTTA GAAGGATTAA AATTCCATTT GTAAAGTCAC  - #                 200                                                                         - - TTTTTAGTGA TCCAACGTTT TCGTTTTGTA G        - #                  - #             231                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:127:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  231 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #127:                        - - CTACAAAACG AAAACGTTGG ATCACTAAAA AGTGACTTTA CAAATGGAAT  - #                  50                                                                         - - TTTAATCCTT CTAAACATAC ACTTTTCTTT TTCTTACAAA GCTCTTCATT  - #                 100                                                                         - - GCAGCAGTCA GGTTGTTTTT CTCTTAAATG CCAAGCTTAA TGGTTCTATT  - #                 150                                                                         - - ACTCAAAAGC CTTCCTACAT AAATTTTTCA TAATTTCGAA GATAACACGT  - #                 200                                                                         - - TACTTTTTTT CCCAAATTAA TCAATTATTA C        - #                  - #             231                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:128:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  78 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #128:                        - - GTTATGTTTT TAACTTTTCT TCGAAGTCAT TAGCGGATTT AATTTTAGAG  - #                  50                                                                         - - AGTTCTTTAT GCCGTGCTTT ATTTATAG         - #                  - #                 78                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:129:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  78 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #129:                        - - CTATAAATAA AGCACGGCAT AAAGAACTCT CTAAAATTAA ATCCGCTAAT  - #                  50                                                                         - - GACTTCGAAG AAAAGTTAAA AACATAAC         - #                  - #                 78                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:130:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  110 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #130:                        - - GTAAGTTTTA CTACAACAAC ACGAAATACT AGAAGAAAAA GACCCGTTAA  - #                  50                                                                         - - TAACTAAAAG TTATGTTCGA AGCAATGAAA TTGTTGCATA TTACTTTCTT  - #                 100                                                                         - - AAAATTACAG                - #                  - #                      - #       110                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:131:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  110 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #131:                        - - CTGTAATTTT AAGAAAGTAA TATGCAACAA TTTCATTGCT TCGAACATAA  - #                  50                                                                         - - CTTTTAGTTA TTAACGGGTC TTTTTCTTCT AGTATTTCGT GTTGTTGTAG  - #                 100                                                                         - - TAAAACTTAC                - #                  - #                      - #       110                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:132:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  89 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #132:                        - - GTATGATGGT CGTAATTAAA ATTTTCTTGG GATTTATGTC NAAAGTTAAT  - #                  50                                                                         - - AAACATATGC ATGCTAAAAA ACATCCGGAA TCTTTTGAG      - #                      - #    89                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:133:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  89 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #133:                        - - CTCAAAAGAT TCCGGATGTT TTTTAGCATG CATATGTTTA TTAACTTTNG  - #                  50                                                                         - - ACATAAATCC CAAGAAAATT TTAATTACGA CCATCATAC      - #                      - #    89                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:134:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  95 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #134:                        - - GTGAGCGAAA TTTTGATACT AAAGAATTTC AGCTTTCTTG ATGGGTGCTG  - #                  50                                                                         - - AAACTTATGG AATATGTAGT CAGAAATAGA TGAAGCTTGC CATAG   - #                      - #95                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:135:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  95 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #135:                        - - CTATGGCAAG CTTCATCTAT TTCTGACTAC ATATTCCATA AGTTTCAGCA  - #                  50                                                                         - - CCCATCAAGA AAGCTGAAAT TCTTTAGTAT CAAAATTTCG CTCAC   - #                      - #95                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:136:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  301 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #136:                        - - GTAAAAAAAG CTTCAGTAAA CTTTAATTTC TCGCTGTGAT TTTGCAGTAT  - #                  50                                                                         - - TGTGAATAAA ATTTTTCTCC GCCTGATTCT TTTGATGAAT CTTAATTTAA  - #                 100                                                                         - - AATAATTTTT GTTACCGCAT GGTATTCCTT TTGTATGATT TGTAACAAAC  - #                 150                                                                         - - AATTTGGAAC ATTTTTTCAA TCGGTGGGTT CGTTTTCAAA ATTACAGAAA  - #                 200                                                                         - - TATTGTGCTA CTGTTACTGA ATGATATTAA ATGCATTTCT GAAAAGGAAT  - #                 250                                                                         - - TATTTCAATG AAATGCTTTC TTAGTTAGAG GCTTACTATA ATTACTTAAA  - #                 300                                                                         - - G                  - #                  - #                  - #                  301                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:137:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  301 nuc - #leotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #137:                        - - CTTTAAGTAA TTATAGTAAG CCTCTAACTA AGAAAGCATT TCATTGAAAT  - #                  50                                                                         - - AATTCCTTTT CAGAAATGCA TTTAATATCA TTCAGTAACA GTAGCACAAT  - #                 100                                                                         - - ATTTCTGTAA TTTTGAAAAC GAACCCACCG ATTGAAAAAA TGTTCCAAAT  - #                 150                                                                         - - TGTTTGTTAC AAATCATACA AAAGGAATAC CATGCGGTAA CAAAAATTAT  - #                 200                                                                         - - TTTAAATTAA GATTCATCAA AAGAATCAGG CGGAGAAAAA TTTTATTCAC  - #                 250                                                                         - - AATACTGCAA AATCACAGCG AGAAATTAAA GTTTACTGAA GCTTTTTTTA  - #                 300                                                                         - - C                  - #                  - #                  - #                  301                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:138:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1056 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..1056                                               - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #138:                        - - GGT GCT AAT GCA GAT GTG GCT ACA GTA CGC GG - #T GAA ACG CCT                 - #  42                                                                    Gly Ala Asn Ala Asp Val Ala Thr Val Arg Gl - #y Glu Thr Pro                   1               5   - #               10                                       - - CTT CAT TTA GCT GCA CGA GCA AAC CAA ACG GA - #C ATT GTT CGT                 - #  84                                                                    Leu His Leu Ala Ala Arg Ala Asn Gln Thr As - #p Ile Val Arg                   15                  - #20                  - #25                               - - GTT TTG GTG CGT AAT GGA GCA CAG GTG GAT GC - #T GCT GCT CGT                 - # 126                                                                    Val Leu Val Arg Asn Gly Ala Gln Val Asp Al - #a Ala Ala Arg                       30              - #    35              - #    40                           - - GAA CTA CAA ACT CCA CTG CAC ATT GCA TCA CG - #T CTT GGT AAT                 - # 168                                                                    Glu Leu Gln Thr Pro Leu His Ile Ala Ser Ar - #g Leu Gly Asn                           45          - #        50          - #        55                       - - ACC GAC ATC GTC ATT TTG TTG CTG CAG GCT AA - #T GCA TCA CCA                 - # 210                                                                    Thr Asp Ile Val Ile Leu Leu Leu Gln Ala As - #n Ala Ser Pro                               60      - #            65      - #            70                   - - AAT GCT GCC ACA AGA GAT CTT TAT ACT CCT CT - #T CAT ATT GCT                 - # 252                                                                    Asn Ala Ala Thr Arg Asp Leu Tyr Thr Pro Le - #u His Ile Ala                                   75  - #                80                                      - - GCC AAG GAG GGG CAA GAG GAA GTG GCA GCA AT - #A TTG ATG GAT                 - # 294                                                                    Ala Lys Glu Gly Gln Glu Glu Val Ala Ala Il - #e Leu Met Asp                   85                  - #90                  - #95                               - - CAT GGA ACC GAC AAG ACA CTG CTC ACG AAA AA - #G GGT TTT ACG                 - # 336                                                                    His Gly Thr Asp Lys Thr Leu Leu Thr Lys Ly - #s Gly Phe Thr                       100              - #   105              - #   110                          - - CCG TTG CAT TTA GCT GCT AAG TAT GGC AAT TT - #G CCG GTC GCG                 - # 378                                                                    Pro Leu His Leu Ala Ala Lys Tyr Gly Asn Le - #u Pro Val Ala                           115          - #       120          - #       125                      - - AAA TCA TTG CTA GAA CGA GGA ACA CCG GTT GA - #C ATT GAA GGC                 - # 420                                                                    Lys Ser Leu Leu Glu Arg Gly Thr Pro Val As - #p Ile Glu Gly                               130      - #           135      - #           140                  - - AAG AAT CAG GTA ACA CCT CTG CAT GTA GCG GC - #A CAT TAC AAT                 - # 462                                                                    Lys Asn Gln Val Thr Pro Leu His Val Ala Al - #a His Tyr Asn                                   145  - #               150                                     - - AAC GAC AAG GTA GCA TTG TTA CTT CTA GAA AA - #T GGT GCT TCT                 - # 504                                                                    Asn Asp Lys Val Ala Leu Leu Leu Leu Glu As - #n Gly Ala Ser                   155                 1 - #60                 1 - #65                            - - GCA CAT GCC GCT GCC AAG AAT GGG TAC ACT CC - #T TTA CAT ATT                 - # 546                                                                    Ala His Ala Ala Ala Lys Asn Gly Tyr Thr Pr - #o Leu His Ile                       170              - #   175              - #   180                          - - GCC GCG AAG AAG AAT CAG ATG GAT ATT GCT AG - #C ACT CTC CTT                 - # 588                                                                    Ala Ala Lys Lys Asn Gln Met Asp Ile Ala Se - #r Thr Leu Leu                           185          - #       190          - #       195                      - - CAT TAT AAG GCA AAT GCG AAT GCT GAA AGC AA - #A GCT GGC TTT                 - # 630                                                                    His Tyr Lys Ala Asn Ala Asn Ala Glu Ser Ly - #s Ala Gly Phe                               200      - #           205      - #           210                  - - ACA CCA CTT CAT CTT GCC GCC CAG GAG GGC CA - #T CGC GAA ATG                 - # 672                                                                    Thr Pro Leu His Leu Ala Ala Gln Glu Gly Hi - #s Arg Glu Met                                   215  - #               220                                     - - GCT GCG TTA TTA ATT GAA AAT GGA GCA AAA GT - #T GGA GCT CAG                 - # 714                                                                    Ala Ala Leu Leu Ile Glu Asn Gly Ala Lys Va - #l Gly Ala Gln                   225                 2 - #30                 2 - #35                            - - GCA AGG AAT GGC TTG ACA CCA ATG CAT TTA TG - #T GCA CAG GAG                 - # 756                                                                    Ala Arg Asn Gly Leu Thr Pro Met His Leu Cy - #s Ala Gln Glu                       240              - #   245              - #   250                          - - GAT CGT GTG AGC GTA GCA GAA GAA CTA GTG AA - #A GAA AAC GCA                 - # 798                                                                    Asp Arg Val Ser Val Ala Glu Glu Leu Val Ly - #s Glu Asn Ala                           255          - #       260          - #       265                      - - GCC ATT GAT CCC AAA ACG AAA GCA GGA TAT AC - #G CCG TTA CAT                 - # 840                                                                    Ala Ile Asp Pro Lys Thr Lys Ala Gly Tyr Th - #r Pro Leu His                               270      - #           275      - #           280                  - - GTT GCT TGC CAT TTT GGA CAA ATA AAC ATG GT - #C CGT TTC TTG                 - # 882                                                                    Val Ala Cys His Phe Gly Gln Ile Asn Met Va - #l Arg Phe Leu                                   285  - #               290                                     - - ATT GAG CAT GGC GCA CGA GTT TCA GTT ATT AC - #T CGT GCT TCC                 - # 924                                                                    Ile Glu His Gly Ala Arg Val Ser Val Ile Th - #r Arg Ala Ser                   295                 3 - #00                 3 - #05                            - - TAT ACT CCT CTG CAT CAA GCT GCT CAG CAA GG - #G CAT AAC AGT                 - # 966                                                                    Tyr Thr Pro Leu His Gln Ala Ala Gln Gln Gl - #y His Asn Ser                       310              - #   315              - #   320                          - - GTT GTA CGT TAC TTG TTG GAA CAT GGT GCA AG - #T CCA AAT GTT                 - #1008                                                                    Val Val Arg Tyr Leu Leu Glu His Gly Ala Se - #r Pro Asn Val                           325          - #       330          - #       335                      - - CAT ACA TCG ACA GGA CAA ACT CCA TTA TCG AT - #T GCT GAA CGT                 - #1050                                                                    His Thr Ser Thr Gly Gln Thr Pro Leu Ser Il - #e Ala Glu Arg                               340      - #           345      - #           350                  - - CTA GGG                - #                  - #                  -      #         1056                                                                  Leu Gly                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:139:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  352 ami - #no acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #139:                        - - Gly Ala Asn Ala Asp Val Ala Thr Val Arg Gl - #y Glu Thr Pro             1               5   - #               10                                       - - Leu His Leu Ala Ala Arg Ala Asn Gln Thr As - #p Ile Val Arg              15                  - #20                  - #25                               - - Val Leu Val Arg Asn Gly Ala Gln Val Asp Al - #a Ala Ala Arg                  30              - #    35              - #    40                           - - Glu Leu Gln Thr Pro Leu His Ile Ala Ser Ar - #g Leu Gly Asn                      45          - #        50          - #        55                       - - Thr Asp Ile Val Ile Leu Leu Leu Gln Ala As - #n Ala Ser Pro                          60      - #            65      - #            70                   - - Asn Ala Ala Thr Arg Asp Leu Tyr Thr Pro Le - #u His Ile Ala                              75  - #                80                                      - - Ala Lys Glu Gly Gln Glu Glu Val Ala Ala Il - #e Leu Met Asp              85                  - #90                  - #95                               - - His Gly Thr Asp Lys Thr Leu Leu Thr Lys Ly - #s Gly Phe Thr                  100              - #   105              - #   110                          - - Pro Leu His Leu Ala Ala Lys Tyr Gly Asn Le - #u Pro Val Ala                      115          - #       120          - #       125                      - - Lys Ser Leu Leu Glu Arg Gly Thr Pro Val As - #p Ile Glu Gly                          130      - #           135      - #           140                  - - Lys Asn Gln Val Thr Pro Leu His Val Ala Al - #a His Tyr Asn                              145  - #               150                                     - - Asn Asp Lys Val Ala Leu Leu Leu Leu Glu As - #n Gly Ala Ser              155                 1 - #60                 1 - #65                            - - Ala His Ala Ala Ala Lys Asn Gly Tyr Thr Pr - #o Leu His Ile                  170              - #   175              - #   180                          - - Ala Ala Lys Lys Asn Gln Met Asp Ile Ala Se - #r Thr Leu Leu                      185          - #       190          - #       195                      - - His Tyr Lys Ala Asn Ala Asn Ala Glu Ser Ly - #s Ala Gly Phe                          200      - #           205      - #           210                  - - Thr Pro Leu His Leu Ala Ala Gln Glu Gly Hi - #s Arg Glu Met                              215  - #               220                                     - - Ala Ala Leu Leu Ile Glu Asn Gly Ala Lys Va - #l Gly Ala Gln              225                 2 - #30                 2 - #35                            - - Ala Arg Asn Gly Leu Thr Pro Met His Leu Cy - #s Ala Gln Glu                  240              - #   245              - #   250                          - - Asp Arg Val Ser Val Ala Glu Glu Leu Val Ly - #s Glu Asn Ala                      255          - #       260          - #       265                      - - Ala Ile Asp Pro Lys Thr Lys Ala Gly Tyr Th - #r Pro Leu His                          270      - #           275      - #           280                  - - Val Ala Cys His Phe Gly Gln Ile Asn Met Va - #l Arg Phe Leu                              285  - #               290                                     - - Ile Glu His Gly Ala Arg Val Ser Val Ile Th - #r Arg Ala Ser              295                 3 - #00                 3 - #05                            - - Tyr Thr Pro Leu His Gln Ala Ala Gln Gln Gl - #y His Asn Ser                  310              - #   315              - #   320                          - - Val Val Arg Tyr Leu Leu Glu His Gly Ala Se - #r Pro Asn Val                      325          - #       330          - #       335                      - - His Thr Ser Thr Gly Gln Thr Pro Leu Ser Il - #e Ala Glu Arg                          340      - #           345      - #           350                  - - Leu Gly                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:140:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  1056 nu - #cleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #140:                        - - CCCTAGACGT TCAGCAATCG ATAATGGAGT TTGTCCTGTC GATGTATGAA  - #                  50                                                                         - - CATTTGGACT TGCACCATGT TCCAACAAGT AACGTACAAC ACTGTTATGC  - #                 100                                                                         - - CCTTGCTGAG CAGCTTGATG CAGAGGAGTA TAGGAAGCAC GAGTAATAAC  - #                 150                                                                         - - TGAAACTCGT GCGCCATGCT CAATCAAGAA ACGGACCATG TTTATTTGTC  - #                 200                                                                         - - CAAAATGGCA AGCAACATGT AACGGCGTAT ATCCTGCTTT CGTTTTGGGA  - #                 250                                                                         - - TCAATGGCTG CGTTTTCTTT CACTAGTTCT TCTGCTACGC TCACACGATC  - #                 300                                                                         - - CTCCTGTGCA CATAAATGCA TTGGTGTCAA GCCATTCCTT GCCTGAGCTC  - #                 350                                                                         - - CAACTTTTGC TCCATTTTCA ATTAATAACG CAGCCATTTC GCGATGGCCC  - #                 400                                                                         - - TCCTGGGCGG CAAGATGAAG TGGTGTAAAG CCAGCTTTGC TTTCAGCATT  - #                 450                                                                         - - CGCATTTGCC TTATAATGAA GGAGAGTGCT AGCAATATCC ATCTGATTCT  - #                 500                                                                         - - TCTTCGCGGC AATATGTAAA GGAGTGTACC CATTCTTGGC AGCGGCATGT  - #                 550                                                                         - - GCAGAAGCAC CATTTTCTAG AAGTAACAAT GCTACCTTGT CGTTATTGTA  - #                 600                                                                         - - ATGTGCCGCT ACATGCAGAG GTGTTACCTG ATTCTTGCCT TCAATGTCAA  - #                 650                                                                         - - CCGGTGTTCC TCGTTCTAGC AATGATTTCG CGACCGGCAA ATTGCCATAC  - #                 700                                                                         - - TTAGCAGCTA AATGCAACGG CGTAAAACCC TTTTTCGTGA GCAGTGTCTT  - #                 750                                                                         - - GTCGGTTCCA TGATCCATCA ATATTGCTGC CACTTCCTCT TGCCCCTCCT  - #                 800                                                                         - - TGGCAGCAAT ATGAAGAGGA GTATAAAGAT CTCTTGTGGC AGCATTTGGT  - #                 850                                                                         - - GATGCATTAG CCTGCAGCAA CAAAATGACG ATGTCGGTAT TACCAAGACG  - #                 900                                                                         - - TGATGCAATG TGCAGTGGAG TTTGTAGTTC ACGAGCAGCA GCATCCACCT  - #                 950                                                                         - - GTGCTCCATT ACGCACCAAA ACACGAACAA TGTCCGTTTG GTTTGCTCGT  - #                1000                                                                         - - GCAGCTAAAT GAAGAGGCGT TTCACCGCGT ACTGTAGCCA CATCTGCATT  - #                1050                                                                         - - AGCACC                 - #                  - #                  -      #         1056                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:141:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:   1266 - #nucleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..1266                                               - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #141:                        - - GCA CGT GGA GGA GCA ATG CGT GGT TGT AGG CA - #T TCC GGT GTC                 - #  42                                                                   Ala Arg Gly Gly Ala Met Arg Gly Cys Arg Hi - #s Ser Gly Val                    1               5  - #                10                                      - - AGA ATC ATT ATA CCA CCG AGG AAA GCG CCG CA - #A CCT ACA CGG                 - #  84                                                                    Arg Ile Ile Ile Pro Pro Arg Lys Ala Pro Gl - #n Pro Thr Arg                   15                  - #20                  - #25                               - - GTC ACA TGC AGA TAC CTT GGA AAG GAC AAG TT - #A GCG CAT CCA                 - # 126                                                                    Val Thr Cys Arg Tyr Leu Gly Lys Asp Lys Le - #u Ala His Pro                       30              - #    35              - #    40                           - - CCA CCA TTA AGT GAA GGT GAA GCG CTC GCN TC - #A CGT ATA CTT                 - # 168                                                                    Pro Pro Leu Ser Glu Gly Glu Ala Leu Ala Se - #r Arg Ile Leu                           45          - #        50          - #        55                       - - GAA ATG GCA CCA CAT GGA GCA AAA TTC TTA GG - #C CCT GTT ATA                 - # 210                                                                    Glu Met Ala Pro His Gly Ala Lys Phe Leu Gl - #y Pro Val Ile                               60      - #            65      - #            70                   - - TTG GAA GTA CCA CAT TTT GCA TCA CTT CGT GG - #A CGA GAG AGA                 - # 252                                                                    Leu Glu Val Pro His Phe Ala Ser Leu Arg Gl - #y Arg Glu Arg                                   75  - #                80                                      - - GAG ATT GTC ATT TTG CGT TCT GAT GAT GGG CA - #G CAT TGG AAA                 - # 294                                                                    Glu Ile Val Ile Leu Arg Ser Asp Asp Gly Gl - #n His Trp Lys                   85                  - #90                  - #95                               - - GAG CAT CAG CTT GAA GCA ACA GAA GAT GCT GT - #A CAA GAG GTG                 - # 336                                                                    Glu His Gln Leu Glu Ala Thr Glu Asp Ala Va - #l Gln Glu Val                       100              - #   105              - #   110                          - - CTC AAT GAA TCG TTT GAT GCA GAA GAG TTG TC - #G CAA CTT GAT                 - # 378                                                                    Leu Asn Glu Ser Phe Asp Ala Glu Glu Leu Se - #r Gln Leu Asp                           115          - #       120          - #       125                      - - GAT TTG CAT ACA TCA CGG ATT ACG CGT ATC CT - #G ACC AAT GAT                 - # 420                                                                    Asp Leu His Thr Ser Arg Ile Thr Arg Ile Le - #u Thr Asn Asp                               130      - #           135      - #           140                  - - TTC CCA ATG TAT TTC GCG GTC GTT ACT CGT GT - #G CGG CAA GAA                 - # 462                                                                    Phe Pro Met Tyr Phe Ala Val Val Thr Arg Va - #l Arg Gln Glu                                   145  - #               150                                     - - GTG CAC TGT GTT GGT CCA GAA GGT GGT GTA AT - #A CTC TCT TCA                 - # 504                                                                    Val His Cys Val Gly Pro Glu Gly Gly Val Il - #e Leu Ser Ser                   155                 1 - #60                 1 - #65                            - - GTT GTT CCT CAT GTG CAG GCC ATA TTT CCG GA - #T GGT TCC TTG                 - # 546                                                                    Val Val Pro His Val Gln Ala Ile Phe Pro As - #p Gly Ser Leu                       170              - #   175              - #   180                          - - ACT AAG ACG ATC AAA GTA TCT GTG CAA GCC CA - #G CCA GTT CCA                 - # 588                                                                    Thr Lys Thr Ile Lys Val Ser Val Gln Ala Gl - #n Pro Val Pro                           185          - #       190          - #       195                      - - CAA GAG ATA GTC ACT CGT TTA CAT GGG AAT AG - #A GTC GCT GTT                 - # 630                                                                    Gln Glu Ile Val Thr Arg Leu His Gly Asn Ar - #g Val Ala Val                               200      - #           205      - #           210                  - - TCT CCA ATT GTA ACT GTT GAA CCG CGT CGT CG - #C AAA TTC CAT                 - # 672                                                                    Ser Pro Ile Val Thr Val Glu Pro Arg Arg Ar - #g Lys Phe His                                   215  - #               220                                     - - AAG CCC ATA ACG CTG TGC ATA CCA TTG CCA CA - #A AGC TCA AAT                 - # 714                                                                    Lys Pro Ile Thr Leu Cys Ile Pro Leu Pro Gl - #n Ser Ser Asn                   225                 2 - #30                 2 - #35                            - - AAA GGA ATG TTA ACA CAA TAT AGT GGC CAA CC - #A GGA CAG GAA                 - # 756                                                                    Lys Gly Met Leu Thr Gln Tyr Ser Gly Gln Pr - #o Gly Gln Glu                       240              - #   245              - #   250                          - - CCA CCG ACG CTG CGT TTA CTC TGC AGT AAA AC - #T GGA GGT TCT                 - # 798                                                                    Pro Pro Thr Leu Arg Leu Leu Cys Ser Lys Th - #r Gly Gly Ser                           255          - #       260          - #       265                      - - TCT CCT GCA CAG TGG GAA GAT ATT ACT GGA AC - #T ACC CAG TTA                 - # 840                                                                    Ser Pro Ala Gln Trp Glu Asp Ile Thr Gly Th - #r Thr Gln Leu                               270      - #           275      - #           280                  - - ACA TTT ACT GGT GAG GAC GTT TCA TTT ACA AC - #T ACG GTT TCT                 - # 882                                                                    Thr Phe Thr Gly Glu Asp Val Ser Phe Thr Th - #r Thr Val Ser                                   285  - #               290                                     - - GCT CGA TTT TGG TTG ATG GAT TGC CAA ACT CC - #G CGA GAT GCG                 - # 924                                                                    Ala Arg Phe Trp Leu Met Asp Cys Gln Thr Pr - #o Arg Asp Ala                   295                 3 - #00                 3 - #05                            - - GCA CGA ATG GCA CAA GAA GTT TAC AAT GAA GC - #A ATT GCA GTT                 - # 966                                                                    Ala Arg Met Ala Gln Glu Val Tyr Asn Glu Al - #a Ile Ala Val                       310              - #   315              - #   320                          - - CCT TAT ATG GCT AAA TTT CTT ATT TTT GCT CG - #A CGA ACT TTT                 - #1008                                                                    Pro Tyr Met Ala Lys Phe Leu Ile Phe Ala Ar - #g Arg Thr Phe                           325          - #       330          - #       335                      - - CCT GCC GAA GGA CAG TTG AGA TTG TTT TGT AT - #G ACT GAT GAT                 - #1050                                                                    Pro Ala Glu Gly Gln Leu Arg Leu Phe Cys Me - #t Thr Asp Asp                               340      - #           345      - #           350                  - - CGG GAA GAT AAA ACC CTG GAA AAA CAA GAA CG - #T TTC ATT GAA                 - #1092                                                                    Arg Glu Asp Lys Thr Leu Glu Lys Gln Glu Ar - #g Phe Ile Glu                                   355  - #               360                                     - - ATT GCG AAA TCG AAA GAT GTA GAA GTC TTA AG - #T GGG CGA CAT                 - #1134                                                                    Ile Ala Lys Ser Lys Asp Val Glu Val Leu Se - #r Gly Arg His                   365                 3 - #70                 3 - #75                            - - CAG TTT TTG GAA TTT TCT GGA AAT CTT CTT CC - #A ATA ACC AAG                 - #1176                                                                    Gln Phe Leu Glu Phe Ser Gly Asn Leu Leu Pr - #o Ile Thr Lys                       380              - #   385              - #   390                          - - AGT GGT GAC CAA CTT TCT CTT TAT TTT CTA CC - #A TTC CAA GAA                 - #1218                                                                    Ser Gly Asp Gln Leu Ser Leu Tyr Phe Leu Pr - #o Phe Gln Glu                           395          - #       400          - #       405                      - - AAT CGT CTT GCT TTC ATG GTA AAG ATA CGC AC - #T CAC ACG GAC                 - #1260                                                                    Asn Arg Leu Ala Phe Met Val Lys Ile Arg Th - #r His Thr Asp                               410      - #           415      - #           420                  - - AAC GAA                - #                  - #                  -      #         1266                                                                  Asn Glu                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:142:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:   422 - #amino acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #142:                        - - Ala Arg Gly Gly Ala Met Arg Gly Cys Arg Hi - #s Ser Gly Val              1               5  - #                10                                      - - Arg Ile Ile Ile Pro Pro Arg Lys Ala Pro Gl - #n Pro Thr Arg              15                  - #20                  - #25                               - - Val Thr Cys Arg Tyr Leu Gly Lys Asp Lys Le - #u Ala His Pro                  30              - #    35              - #    40                           - - Pro Pro Leu Ser Glu Gly Glu Ala Leu Ala Se - #r Arg Ile Leu                      45          - #        50          - #        55                       - - Glu Met Ala Pro His Gly Ala Lys Phe Leu Gl - #y Pro Val Ile                          60      - #            65      - #            70                   - - Leu Glu Val Pro His Phe Ala Ser Leu Arg Gl - #y Arg Glu Arg                              75  - #                80                                      - - Glu Ile Val Ile Leu Arg Ser Asp Asp Gly Gl - #n His Trp Lys              85                  - #90                  - #95                               - - Glu His Gln Leu Glu Ala Thr Glu Asp Ala Va - #l Gln Glu Val                  100              - #   105              - #   110                          - - Leu Asn Glu Ser Phe Asp Ala Glu Glu Leu Se - #r Gln Leu Asp                      115          - #       120          - #       125                      - - Asp Leu His Thr Ser Arg Ile Thr Arg Ile Le - #u Thr Asn Asp                          130      - #           135      - #           140                  - - Phe Pro Met Tyr Phe Ala Val Val Thr Arg Va - #l Arg Gln Glu                              145  - #               150                                     - - Val His Cys Val Gly Pro Glu Gly Gly Val Il - #e Leu Ser Ser              155                 1 - #60                 1 - #65                            - - Val Val Pro His Val Gln Ala Ile Phe Pro As - #p Gly Ser Leu                  170              - #   175              - #   180                          - - Thr Lys Thr Ile Lys Val Ser Val Gln Ala Gl - #n Pro Val Pro                      185          - #       190          - #       195                      - - Gln Glu Ile Val Thr Arg Leu His Gly Asn Ar - #g Val Ala Val                          200      - #           205      - #           210                  - - Ser Pro Ile Val Thr Val Glu Pro Arg Arg Ar - #g Lys Phe His                              215  - #               220                                     - - Lys Pro Ile Thr Leu Cys Ile Pro Leu Pro Gl - #n Ser Ser Asn              225                 2 - #30                 2 - #35                            - - Lys Gly Met Leu Thr Gln Tyr Ser Gly Gln Pr - #o Gly Gln Glu                  240              - #   245              - #   250                          - - Pro Pro Thr Leu Arg Leu Leu Cys Ser Lys Th - #r Gly Gly Ser                      255          - #       260          - #       265                      - - Ser Pro Ala Gln Trp Glu Asp Ile Thr Gly Th - #r Thr Gln Leu                          270      - #           275      - #           280                  - - Thr Phe Thr Gly Glu Asp Val Ser Phe Thr Th - #r Thr Val Ser                              285  - #               290                                     - - Ala Arg Phe Trp Leu Met Asp Cys Gln Thr Pr - #o Arg Asp Ala              295                 3 - #00                 3 - #05                            - - Ala Arg Met Ala Gln Glu Val Tyr Asn Glu Al - #a Ile Ala Val                  310              - #   315              - #   320                          - - Pro Tyr Met Ala Lys Phe Leu Ile Phe Ala Ar - #g Arg Thr Phe                      325          - #       330          - #       335                      - - Pro Ala Glu Gly Gln Leu Arg Leu Phe Cys Me - #t Thr Asp Asp                          340      - #           345      - #           350                  - - Arg Glu Asp Lys Thr Leu Glu Lys Gln Glu Ar - #g Phe Ile Glu                              355  - #               360                                     - - Ile Ala Lys Ser Lys Asp Val Glu Val Leu Se - #r Gly Arg His              365                 3 - #70                 3 - #75                            - - Gln Phe Leu Glu Phe Ser Gly Asn Leu Leu Pr - #o Ile Thr Lys                  380              - #   385              - #   390                          - - Ser Gly Asp Gln Leu Ser Leu Tyr Phe Leu Pr - #o Phe Gln Glu                      395          - #       400          - #       405                      - - Asn Arg Leu Ala Phe Met Val Lys Ile Arg Th - #r His Thr Asp                          410      - #           415      - #           420                  - - Asn Glu                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:143:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:   1266 - #nucleotides                                             (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #143:                        - - TTCGTTGTCC GTGTGAGTGC GTATCTTTAC CATGAAAGCA AGACGATTTT  - #                  50                                                                         - - CTTGGAATGG TAGAAAATAA AGAGAAAGTT GGTCACCACT CTTGGTTATT  - #                 100                                                                         - - GGAAGAAGAT TTCCAGAAAA TTCCAAAAAC TGATGTCGCC CACTTAAGAC  - #                 150                                                                         - - TTCTACATCT TTCGATTTCG CAATTTCAAT GAAACGTTCT TGTTTTTCCA  - #                 200                                                                         - - GGGTTTTATC TTCCCGATCA TCAGTCATAC AAAACAATCT CAACTGTCCT  - #                 250                                                                         - - TCGGCAGGAA AAGTTCGTCG AGCAAAAATA AGAAATTTAG CCATATAAGG  - #                 300                                                                         - - AACTGCAATT GCTTCATTGT AAACTTCTTG TGCCATTCGT GCCGCATCTC  - #                 350                                                                         - - GCGGAGTTTG GCAATCCATC AACCAAAATC GAGCAGAAAC CGTAGTTGTA  - #                 400                                                                         - - AATGAAACGT CCTCACCAGT AAATGTTAAC TGGGTAGTTC CAGTAATATC  - #                 450                                                                         - - TTCCCACTGT GCAGGAGAAG AACCTCCAGT TTTACTGCAG AGTAAACGCA  - #                 500                                                                         - - GCGTCGGTGG TTCCTGTCCT GGTTGGCCAC TATATTGTGT TAACATTCCT  - #                 550                                                                         - - TTATTTGAGC TTTGTGGCAA TGGTATGCAC AGCGTTATGG GCTTATGGAA  - #                 600                                                                         - - TTTGCGACGA CGCGGTTCAA CAGTTACAAT TGGAGAAACA GCGACTCTAT  - #                 650                                                                         - - TCCCATGTAA ACGAGTGACT ATCTCTTGTG GAACTGGCTG GGCTTGCACA  - #                 700                                                                         - - GATACTTTGA TCGTCTTAGT CAAGGAACCA TCCGGAAATA TGGCCTGCAC  - #                 750                                                                         - - ATGAGGAACA ACTGAAGAGA GTATTACACC ACCTTCTGGA CCAACACAGT  - #                 800                                                                         - - GCACTTCTTG CCGCACACGA GTAACGACCG CGAAATACAT TGGGAAATCA  - #                 850                                                                         - - TTGGTCAGGA TACGCGTAAT CCGTGATGTA TGCAAATCAT CAAGTTGCGA  - #                 900                                                                         - - CAACTCTTCT GCATCAAACG ATTCATTGAG CACCTCTTGT ACAGCATCTT  - #                 950                                                                         - - CTGTTGCTTC AAGCTGATGC TCTTTCCAAT GCTGCCCATC ATCAGAACGC  - #                1000                                                                         - - AAAATGACAA TCTCTCTCTC TCGTCCACGA AGTGATGCAA AATGTGGTAC  - #                1050                                                                         - - TTCCAATATA ACAGGGCCTA AGAATTTTGC TCCATGTGGT GCCATTTCAA  - #                1100                                                                         - - GTATACGTGA NGCGAGCGCT TCACCTTCAC TTAATGGTGG TGGATGCGCT  - #                1150                                                                         - - AACTTGTCCT TTCCAAGGTA TCTGCATGTG ACCCGTGTAG GTTGCGGCGC  - #                1200                                                                         - - TTTCCTCGGT GGTATAATGA TTCTGACACC GGAATGCCTA CAACCACGCA  - #                1250                                                                         - - TTGCTCCTCC ACGTGC             - #                  - #                      - #  1266                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:144:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:   864 - #nucleotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  CDS                                                            (B) LOCATION:  1..861                                                - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #144:                        - - CAA CTA GTT GGT CTT GAA GCA GTC ACT ATT CT - #A CGT ATT TGG                 - #  42                                                                    Gln Leu Val Gly Leu Glu Ala Val Thr Ile Le - #u Arg Ile Trp                    1               5  - #                10                                      - - ATA TTT TTG AAG AAA GAA CAA GCT ACG CCC GT - #T GCT TTG CGA                 - #  84                                                                    Ile Phe Leu Lys Lys Glu Gln Ala Thr Pro Va - #l Ala Leu Arg                   15                  - #20                  - #25                               - - TCA GCA TTG CAG CGA ATA GGA CGT GAT GAT GT - #T GTA CGA GAA                 - # 126                                                                    Ser Ala Leu Gln Arg Ile Gly Arg Asp Asp Va - #l Val Arg Glu                       30              - #    35              - #    40                           - - ATG GAT CGA GCT GAA AAG CTA GAT GGT TTA GA - #A GGA ACA CCT                 - # 168                                                                    Met Asp Arg Ala Glu Lys Leu Asp Gly Leu Gl - #u Gly Thr Pro                           45          - #        50          - #        55                       - - GTA TCG CAT ATT TCT GGA CCC TCA ATA ACT CT - #G TCA TCT ACT                 - # 210                                                                    Val Ser His Ile Ser Gly Pro Ser Ile Thr Le - #u Ser Ser Thr                               60      - #            65      - #            70                   - - TTG CTA GAG GTA GCA GGC GAC AGA CGT CGT CA - #C GCC GAG GTA                 - # 252                                                                    Leu Leu Glu Val Ala Gly Asp Arg Arg Arg Hi - #s Ala Glu Val                                   75  - #                80                                      - - ACA ATG GCG CAA CAG CGA TTG GCA CAA GAA CC - #G TTT TTT CAG                 - # 294                                                                    Thr Met Ala Gln Gln Arg Leu Ala Gln Glu Pr - #o Phe Phe Gln                   85                  - #90                  - #95                               - - CAA GTA GGG TAT AAT GGG ACA CCT GGA GAT CC - #A GAA GAA CCC                 - # 336                                                                    Gln Val Gly Tyr Asn Gly Thr Pro Gly Asp Pr - #o Glu Glu Pro                       100              - #   105              - #   110                          - - AAA GAA CAG TCA TTC CAC GAA GAG GAA GAG GA - #A GTT GCA GTT                 - # 378                                                                    Lys Glu Gln Ser Phe His Glu Glu Glu Glu Gl - #u Val Ala Val                           115          - #       120          - #       125                      - - TCA GAA ATT CGA ACA GTT GTG CGC ACT GAA CG - #A CAT GTG CAT                 - # 420                                                                    Ser Glu Ile Arg Thr Val Val Arg Thr Glu Ar - #g His Val His                               130      - #           135      - #           140                  - - GAT TCG GAA AAT GGT CCT ATT GTG GAA GAG CG - #T ACA ATA ACA                 - # 462                                                                    Asp Ser Glu Asn Gly Pro Ile Val Glu Glu Ar - #g Thr Ile Thr                                   145  - #               150                                     - - ACT ACG TAT GAG GAT GAT GTT GCT GTA AAC GA - #A GAA GAA ATT                 - # 504                                                                    Thr Thr Tyr Glu Asp Asp Val Ala Val Asn Gl - #u Glu Glu Ile                   155                 1 - #60                 1 - #65                            - - GTT GAC AAA ATA GTG CCT CTC AAC GAA GAG GA - #G CAA GAA AAA                 - # 546                                                                    Val Asp Lys Ile Val Pro Leu Asn Glu Glu Gl - #u Gln Glu Lys                       170              - #   175              - #   180                          - - TGG GAT CGA ATG GTT CGA GAA GTG GAA ATG AA - #T TTT GAG CAA                 - # 588                                                                    Trp Asp Arg Met Val Arg Glu Val Glu Met As - #n Phe Glu Gln                           185          - #       190          - #       195                      - - CAA GAA ACA TCA AAA GAA GGA ACG TTT GGT TG - #T CAG ACA ACA                 - # 630                                                                    Gln Glu Thr Ser Lys Glu Gly Thr Phe Gly Cy - #s Gln Thr Thr                               200      - #           205      - #           210                  - - CAT GAG AAA GAA AAA GAT GAT GAT GGT GGC AG - #T CTG AAG ACG                 - # 672                                                                    His Glu Lys Glu Lys Asp Asp Asp Gly Gly Se - #r Leu Lys Thr                                   215  - #               220                                     - - ACA ATG AAA GAT AGT CAC GTA AGG CAG ATT TT - #C TTC GAT GGA                 - # 714                                                                    Thr Met Lys Asp Ser His Val Arg Gln Ile Ph - #e Phe Asp Gly                   225                 2 - #30                 2 - #35                            - - GGT GAG ACA TCC GCT AAT GAA ACA GGA TTA AG - #T AGC GGG GAT                 - # 756                                                                    Gly Glu Thr Ser Ala Asn Glu Thr Gly Leu Se - #r Ser Gly Asp                       240              - #   245              - #   250                          - - GCA GAC ACT ATT ATG ACT CCA ACG ACA AAG GA - #G GAT AAT CAT                 - # 798                                                                    Ala Asp Thr Ile Met Thr Pro Thr Thr Lys Gl - #u Asp Asn His                           255          - #       260          - #       265                      - - GTT ATA GAC GTA ATG GAG GAA AGG CGA ACT GA - #T GAA GAG GCC                 - # 840                                                                    Val Ile Asp Val Met Glu Glu Arg Arg Thr As - #p Glu Glu Ala                               270      - #           275      - #           280                  - - AAA GGG CAA AGC GTT CAT GAA TAA     - #                  - #                   864                                                                     Lys Gly Gln Ser Val His Glu                                                                   285                                                            - -  - - (2) INFORMATION FOR SEQ ID NO:145:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:   287 - #amino acids                                              (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #145:                        - - Gln Leu Val Gly Leu Glu Ala Val Thr Ile Le - #u Arg Ile Trp               1               5  - #                10                                      - - Ile Phe Leu Lys Lys Glu Gln Ala Thr Pro Va - #l Ala Leu Arg              15                  - #20                  - #25                               - - Ser Ala Leu Gln Arg Ile Gly Arg Asp Asp Va - #l Val Arg Glu                  30              - #    35              - #    40                           - - Met Asp Arg Ala Glu Lys Leu Asp Gly Leu Gl - #u Gly Thr Pro                      45          - #        50          - #        55                       - - Val Ser His Ile Ser Gly Pro Ser Ile Thr Le - #u Ser Ser Thr                          60      - #            65      - #            70                   - - Leu Leu Glu Val Ala Gly Asp Arg Arg Arg Hi - #s Ala Glu Val                              75  - #                80                                      - - Thr Met Ala Gln Gln Arg Leu Ala Gln Glu Pr - #o Phe Phe Gln              85                  - #90                  - #95                               - - Gln Val Gly Tyr Asn Gly Thr Pro Gly Asp Pr - #o Glu Glu Pro                  100              - #   105              - #   110                          - - Lys Glu Gln Ser Phe His Glu Glu Glu Glu Gl - #u Val Ala Val                      115          - #       120          - #       125                      - - Ser Glu Ile Arg Thr Val Val Arg Thr Glu Ar - #g His Val His                          130      - #           135      - #           140                  - - Asp Ser Glu Asn Gly Pro Ile Val Glu Glu Ar - #g Thr Ile Thr                              145  - #               150                                     - - Thr Thr Tyr Glu Asp Asp Val Ala Val Asn Gl - #u Glu Glu Ile              155                 1 - #60                 1 - #65                            - - Val Asp Lys Ile Val Pro Leu Asn Glu Glu Gl - #u Gln Glu Lys                  170              - #   175              - #   180                          - - Trp Asp Arg Met Val Arg Glu Val Glu Met As - #n Phe Glu Gln                      185          - #       190          - #       195                      - - Gln Glu Thr Ser Lys Glu Gly Thr Phe Gly Cy - #s Gln Thr Thr                          200      - #           205      - #           210                  - - His Glu Lys Glu Lys Asp Asp Asp Gly Gly Se - #r Leu Lys Thr                              215  - #               220                                     - - Thr Met Lys Asp Ser His Val Arg Gln Ile Ph - #e Phe Asp Gly              225                 2 - #30                 2 - #35                            - - Gly Glu Thr Ser Ala Asn Glu Thr Gly Leu Se - #r Ser Gly Asp                  240              - #   245              - #   250                          - - Ala Asp Thr Ile Met Thr Pro Thr Thr Lys Gl - #u Asp Asn His                      255          - #       260          - #       265                      - - Val Ile Asp Val Met Glu Glu Arg Arg Thr As - #p Glu Glu Ala                          270      - #           275      - #           280                  - - Lys Gly Gln Ser Val His Glu                                                              285                                                            - -  - - (2) INFORMATION FOR SEQ ID NO:146:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:   864 - #nucleotides                                              (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  cDNA                                             - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #146:                        - - TTATTCATGA ACGCTTTGCC CTTTGGCCTC TTCATCAGTT CGCCTTTCCT  - #                  50                                                                         - - CCATTACGTC TATAACATGA TTATCCTCCT TTGTCGTTGG AGTCATAATA  - #                 100                                                                         - - GTGTCTGCAT CCCCGCTACT TAATCCTGTT TCATTAGCGG ATGTCTCACC  - #                 150                                                                         - - TCCATCGAAG AAAATCTGCC TTACGTGACT ATCTTTCATT GTCGTCTTCA  - #                 200                                                                         - - GACTGCCACC ATCATCATCT TTTTCTTTCT CATGTGTTGT CTGACAACCA  - #                 250                                                                         - - AACGTTCCTT CTTTTGATGT TTCTTGTTGC TCAAAATTCA TTTCCACTTC  - #                 300                                                                         - - TCGAACCATT CGATCCCATT TTTCTTGCTC CTCTTCGTTG AGAGGCACTA  - #                 350                                                                         - - TTTTGTCAAC AATTTCTTCT TCGTTTACAG CAACATCATC CTCATACGTA  - #                 400                                                                         - - GTTGTTATTG TACGCTCTTC CACAATAGGA CCATTTTCCG AATCATGCAC  - #                 450                                                                         - - ATGTCGTTCA GTGCGCACAA CTGTTCGAAT TTCTGAAACT GCAACTTCCT  - #                 500                                                                         - - CTTCCTCTTC GTGGAATGAC TGTTCTTTGG GTTCTTCTGG ATCTCCAGGT  - #                 550                                                                         - - GTCCCATTAT ACCCTACTTG CTGAAAAAAC GGTTCTTGTG CCAATCGCTG  - #                 600                                                                         - - TTGCGCCATT GTTACCTCGG CGTGACGACG TCTGTCGCCT GCTACCTCTA  - #                 650                                                                         - - GCAAAGTAGA TGACAGAGTT ATTGAGGGTC CAGAAATATG CGATACAGGT  - #                 700                                                                         - - GTTCCTTCTA AACCATCTAG CTTTTCAGCT CGATCCATTT CTCGTACAAC  - #                 750                                                                         - - ATCATCACGT CCTATTCGCT GCAATGCTGA TCGCAAAGCA ACGGGCGTAG  - #                 800                                                                         - - CTTGTTCTTT CTTCAAAAAT ATCCAAATAC GTAGAATAGT GACTGCTTCA  - #                 850                                                                         - - AGACCAACTA GTTG              - #                  - #                      - #    864                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:147:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  34 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #147:                        - - CGCGGATCCG CATGAGTAAT CCTATAGTCG AGGG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:148:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #148:                        - - TACAACAGAT TCGTGATTTT C           - #                  - #                      - #21                                                                  - - (2) INFORMATION FOR SEQ ID NO:149:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  18 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #149:                        - - GTGACTTCGA AAAGCGGC             - #                  - #                      - #  18                                                                   - - (2) INFORMATION FOR SEQ ID NO:150:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  24 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #150:                        - - GAACTAGTGA AAGAAAACGC AGCC          - #                  - #                    24                                                                      - - (2) INFORMATION FOR SEQ ID NO:151:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  24 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #151:                        - - GTAACGTACA ACACTGTTAT GCCC          - #                  - #                    24                                                                      - - (2) INFORMATION FOR SEQ ID NO:152:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  24 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #152:                        - - GGTGAAGATA ATCAGATCAC AGCC          - #                  - #                    24                                                                      - - (2) INFORMATION FOR SEQ ID NO:153:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #153:                        - - CGATGCATCT AAGGAAGGAT C           - #                  - #                      - #21                                                                   - - (2) INFORMATION FOR SEQ ID NO:154:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #154:                        - - GATCCTTCCT TAGATGCATC G           - #                  - #                      - #21                                                                   - - (2) INFORMATION FOR SEQ ID NO:155:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  24 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #155:                        - - CGGTGGTATA ATGATTCTGA CACC          - #                  - #                    24                                                                      - - (2) INFORMATION FOR SEQ ID NO:156:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  27 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #156:                        - - CTCTCTCTCT CGTCCACGAA GTGATGC          - #                  - #                 27                                                                      - - (2) INFORMATION FOR SEQ ID NO:157:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  18 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #157:                        - - CGCACTGAAC GACATGTG             - #                  - #                      - #  18                                                                   - - (2) INFORMATION FOR SEQ ID NO:158:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #158:                        - - CTCATGTGTT GTCTGACAAC C           - #                  - #                      - #21                                                                   - - (2) INFORMATION FOR SEQ ID NO:159:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #159:                        - - GGATTAAGTA GCGGGGATGC A           - #                  - #                      - #21                                                                   - - (2) INFORMATION FOR SEQ ID NO:160:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  21 nucl - #eotides                                               (B) TYPE:  nucleic a - #cid                                                   (C) STRANDEDNESS:  sing - #le                                                 (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Primer                                           - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #160:                        - - GCAACATAGG CATGTGCGAG A           - #                  - #                      - #21                                                                   - - (2) INFORMATION FOR SEQ ID NO:161:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  34 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #161:                        - - Met Ser Asn Pro Ile Val Glu Gly Ser Gly Tr - #p Pro Ala Glu               1               5  - #                10                                      - - Pro Lys Asp Ser Gln His Gln Gln Gln Ile Pr - #o Asp Asp Asn              15                  - #20                  - #25                               - - Ser Gln His Ser Asn Lys                                                      30                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:162:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  67 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #162:                        - - Gly Glu Ser Ser Ala Ser Phe Leu Arg Ala Al - #a Arg Ala Gly               1               5  - #                10                                      - - Asn Leu Asp Arg Val Leu Glu Leu Leu Arg Se - #r Gly Thr Asp              15                  - #20                  - #25                               - - Ile Asn Thr Cys Asn Ala Asn Gly Leu Asn Al - #a Leu His Leu                  30              - #    35              - #    40                           - - Ala Ser Lys Glu Gly His His Glu Val Val Ar - #g Glu Leu Leu                      45          - #        50          - #        55                       - - Lys Arg Lys Ala Asp Val Asp Ala Ala Thr Ar - #g                                      60      - #            65                                          - -  - - (2) INFORMATION FOR SEQ ID NO:163:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  62 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #163:                        - - Pro Leu His Val Ala Thr Lys Trp Gly Arg Th - #r Asn Met                   1               5  - #                10                                      - - Val Ser Leu Leu Leu Ala His Gly Ala Val Il - #e Asp Cys Arg              15                  - #20                  - #25                               - - Thr Arg Asp Leu Leu Thr Pro Leu His Cys Al - #a Ser Arg Ser                  30              - #    35              - #    40                           - - Gly His Asp Gln Val Val Asp Leu Leu Leu Gl - #u Lys Gly Ala                      45          - #        50          - #        55                       - - Pro Ile Ser Ala Lys Thr Lys                                                          60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:164:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  11 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #164:                        - - Asn Gly Leu Ala Pro Leu His Met Ala Ala Gl - #n                           1               5  - #                10                                      - - (2) INFORMATION FOR SEQ ID NO:165:                                        - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  50 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #165:                        - - Val Asp Ala Ala Ala Arg Glu Leu Gln Thr Pr - #o Leu His Ile               1               5  - #                10                                      - - Ala Ser Arg Leu Gly Asn Thr Asp Ile Val Il - #e Leu Leu Leu              15                  - #20                  - #25                               - - Gln Ala Asn Ala Ser Pro Asn Ala Ala Thr Ar - #g Asp Leu Tyr                  30              - #    35              - #    40                           - - Thr Pro Leu His Ile Ala Ala Lys                                                  45          - #        50                                              - -  - - (2) INFORMATION FOR SEQ ID NO:166:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  53 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #166:                        - - Gln Ile Asn Met Val Arg Phe Leu Ile Glu Hi - #s Gly Ala                   1               5  - #                10                                      - - Arg Val Ser Val Ile Thr Arg Ala Ser Tyr Th - #r Pro Leu His              15                  - #20                  - #25                               - - Gln Ala Ala Gln Gln Gly His Asn Ser Val Va - #l Arg Tyr Leu                  30              - #    35              - #    40                           - - Leu Glu His Gly Ala Ser Pro Asn Val His Th - #r Ser                              45          - #        50                                              - -  - - (2) INFORMATION FOR SEQ ID NO:167:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  44 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #167:                        - - Phe Leu Ile Ser Phe Met Val Asp Ala Arg Gl - #y Gly Ala Met               1               5  - #                10                                      - - Arg Gly Cys Arg His Ser Gly Val Arg Ile Il - #e Ile Pro Pro              15                  - #20                  - #25                               - - Arg Lys Ala Pro Gln Pro Thr Arg Val Thr Cy - #s Arg Tyr Leu                  30              - #    35              - #    40                           - - Gly Lys                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:168:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  59 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #168:                        - - Val Ala Leu Arg Ser Ala Leu Gln Arg Ile Gl - #y Arg Asp                   1               5  - #                10                                      - - Asp Val Val Arg Glu Met Asp Arg Ala Glu Ly - #s Leu Asp Gly              15                  - #20                  - #25                               - - Leu Glu Gly Thr Pro Val Ser His Ile Ser Gl - #y Pro Ser Ile                  30              - #    35              - #    40                           - - Thr Leu Ser Ser Thr Leu Leu Glu Val Ala Gl - #y Asp Arg Arg                      45          - #        50          - #        55                       - - Arg His Ala Glu                                                           - -  - - (2) INFORMATION FOR SEQ ID NO:169:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  61 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #169:                        - - Val Thr Met Ala Gln Gln Arg Leu Ala Gln Gl - #u Pro Phe Phe               1               5  - #                10                                      - - Gln Gln Val Gly Tyr Asn Gly Thr Pro Gly As - #p Pro Glu Glu              15                  - #20                  - #25                               - - Pro Lys Glu Gln Ser Phe His Glu Glu Glu Gl - #u Glu Val Ala                  30              - #    35              - #    40                           - - Val Ser Glu Ile Arg Thr Val Val Arg Thr Gl - #u Arg His Val                      45          - #        50          - #        55                       - - His Asp Ser Glu Asn                                                                  60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:170:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  52 amin - #o acids                                               (B) TYPE:  amino aci - #d                                                     (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #170:                        - - Pro Ile Val Glu Glu Arg Thr Ile Thr Thr Th - #r Tyr Glu                   1               5  - #                10                                      - - Asp Asp Val Ala Val Asn Glu Glu Glu Ile Va - #l Asp Lys Ile              15                  - #20                  - #25                               - - Val Pro Leu Asn Glu Glu Glu Gln Glu Lys Tr - #p Asp Arg Met                  30              - #    35              - #    40                           - - Val Arg Glu Val Glu Met Asn Phe Glu Gln Gl - #n                                  45          - #        50                                              - -  - - (2) INFORMATION FOR SEQ ID NO:171:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH:  18 amin - #o acids                                               (B) TYPE:  amino sin - #gle                                                   (D) TOPOLOGY:  linear                                                - -     (ii) MOLECULE TYPE:  Protein                                          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #171:                        - - Val Met Glu Glu Arg Arg Thr Asp Glu Glu Al - #a Lys Gly                   1               5  - #                10                                      - - Gln Ser Val His Glu                                                     __________________________________________________________________________

While various embodiments of the present invention have been describedin detail, it is apparent that modifications and adaptations of thoseembodiments will occur to those skilled in the art. It is to beexpressly understood, however, that such modifications and adaptationsare within the scope of the present invention, as set forth in thefollowing claims.

What is claimed is:
 1. An isolated ankyrin nucleic acid molecule whereinsaid nucleic acid molecule is a Dirofilaria or Brugia nucleic acidmolecule that hybridizes to a nucleic acid molecule having a nucleicacid sequence selected from the group consisting of SEQ ID NO:86, SEQ IDNO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ IDNO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ IDNO:97, SEQ ID NO:98, SEQ ID NO:99, SEO ID NO:100, SEQ ID NO:101, SEQ IDNO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQID NO:107, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114,SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ IDNO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQID NO:134, SEQ ID NO:136; SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:141,SEQ ID NO:143, SEQ ID NO:144 and SEQ ID NO:146 under conditionscomprising (a) hybridizing in a solution comprising 2×SSC and 0%formamide, at a temperature of 37° C., and (b) washing in 1×SSC and 0%formamide at a temperature of 49° C.
 2. The ankyrin nucleic acidmolecule of claim 1, wherein said nucleic acid molecule is selected fromthe group consisting of a Dirofilaria immitis ankyrin nucleic acidmolecule and a Brugia malayi ankyrin nucleic acid molecule.
 3. Theankyrin nucleic acid molecule of claim 1, wherein said nucleic acidmolecule comprises a nucleic acid sequence selected from the groupconsisting of: a nucleic acid sequence selected from the groupconsisting of SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89,SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94,SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99,SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ IDNO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118,SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ IDNO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136; SEQID NO:138, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:144,and SEQ ID NO:146; and an allelic variant of a nucleic acid sequenceselected from the group consisting of the above-listed sequences.
 4. Theankyrin nucleic acid molecule of claim 1, wherein said ankyrin nucleicacid molecule comprises a nucleic acid sequence that encodes an ankyrinprotein.
 5. The ankyrin nucleic acid molecule of claim 1, wherein saidnucleic acid molecule is selected from the group consisting of: anucleic acid molecule selected from the group consisting of DiAnk-int₉₂,DiAnk-int₁₁₈, DiAnk-int₂₄₈, DiAnk-int₉₄, DiAnk-int₄₈, DiAnk-int₂₀₀,DiAnk-int₈₂, DiAnk-int₂₁₃, DiAnk-int₇₆, DiAnk-int₂₃₁, DiAnk-int₇₈,DiAnk-int₁₁₀, DiAnk-int₈₉, DiAnk-int₉₅, DiAnk-int₃₀₁, DiAnk-ex₁₀₂,DiAnk-ex₂₀₁, DiAnk-ex₁₈₇, DiAnk-ex₃₄, DiAnk-ex₁₅₀, DiAnk-ex₁₆₁,DiAnk-ex₁₃₃, DiAnk-ex₁₇₉, DiAnk-ex₁₈₄, DiAnk-ex₁₅₈, DiAnk-ex₅₉,nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, and nDiAnk₈₆₄ ; and an allelic variant of anucleic acid molecule selected from the group consisting of DiAnk-int₉₂,DiAnk-int₁₁₈, DiAnk-int₂₄₈, DiAnk-int₉₄, DiAnk-int₄₈, DiAnk-int₂₀₀,DiAnk-int₈₂, DiAnk-int₂₁₃, DiAnk-int₇₆, DiAnk-int₂₃₁, DiAnk-int₇₈,DiAnk-int₁₁₀, DiAnk-int₈₉, DiAnk-int₉₅, DiAnk-int₃₀₁, DiAnk-ex₁₀₂,DiAnk-ex₂₀₁, DiAnk-ex₁₈₇, DiAnk-ex₃₄, DiAnk-ex₁₅₀, DiAnk-ex161,DiAnk-ex₁₃₃, DiAnk-ex₁₇₉, DiAnk-ex₁₈₄, DiAnk-ex₁₅₈, DiAnk-ex₅₉,nDiAnk₁₀₅₆, nDiAnk₁₂₆₆, and nDiAnk₈₆₄.
 6. The ankyrin nucleic acidmolecule of claim 1, wherein said nucleic acid molecule encodcs aprotein selected from the group consisting of a protein that shares atleast about 85% identity with PDiANK₃₅₂, a protein that shares at leastabout 95% identity with PDiAnk₄₂₂, and a protein that shares at leastabout 80% identity with PDiANK₂₈₈.
 7. The ankyrin nucleic acid moleculeof claim 1, wherein said nucleic acid molecule encodes a proteincomprising an amino acid sequence selected from the group consisting ofan amino acid sequence that shares at least about 85% identity with SEQID NO:139, an amino acid sequence that shares at least about 95%identity with SEQ ID NO:142, an amino acid sequence that shares at leastabout 75% identity with SEQ ID NO:145, an amino acid sequence thatshares at least about 75% identity with SEQ ID NO:161, an amino acidsequence that shares at least about 85% identity with SEQ ID NO:162, anamino acid sequence that shares at least about 85% identity with SEQ IDNO:163, an amino acid sequence that shares at least about 100% identitywith SEQ ID NO:164, an amino acid sequence that shares at least about90% identity with SEQ ID NO:165, an amino acid sequence that shares atleast about 75% identity with SEQ ID NO:166, an amino acid sequence thatshares at least about 90% identity with SEQ ID NO:167, an amino acidsequence that shares at least about 80% identity with SEQ ID NO:168, anamino acid sequence that shares at least about 95% identity with SEQ IDNO:169, an amino acid sequence that shares at least about 75% identitywith SEQ ID NO:170, and an amino acid sequence that shares at leastabout 95% identity with SEQ ID NO:171.
 8. The ankyrin nucleic acidmolecule of claim 1, wherein said nucleic acid molecule is selected fromthe group consisting of: a nucleic acid molecule encoding a proteincomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:139, SEQ ID NO:142, SEQ ID NO:145, SEQ ID NO:161, SEQ IDNO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, and SEQ IDNO:171; and an allelic variant of a nucleic acid molecule encoding aprotein comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:139, SEQ ID NO:142, SEQ ID NO:145, SEQ IDNO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170,and SEQ ID NO:171.
 9. A recombinant molecule comprising an ankyrinnucleic acid molecule as set forth in claim 1 operatively linked to atranscription control sequence.
 10. A recombinant virus comprising anankyrin nucleic acid molecule as set forth in claim
 1. 11. A recombinantcell comprising an ankyrin nucleic acid molecule as set forth inclaim
 1. 12. An isolated ankyrin nucleic acid molecule that hybridizesto a nucleic acid molecule having a nucleic acid sequence selected fromthe group consisting of SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ IDNO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ IDNO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ IDNO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108,SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ IDNO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136;SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:143, SEQ IDNO:144 and SEQ ID NO:146 underhybridization and wash conditions whichallow 30% or less base-pair mismatch, wherein such conditions aredetermined by a formula:

    T.sub.m =81.5° C.+16.6 log M+0.41(% G+C)-500/n-0.61 (% formamide),

wherein T_(m) represents the temperature at which two complementarynucleic acid molecule strands will disassociate, assuming 100%complementarity between the two strands, n represents the number ofnucleotides in the shorter strand of the duplex being hybridized and logM represents the ionic strengths of the hybridization and wash solutionsin moles/liter; wherein said wash is conducted at a temperature of T_(m)minus 30° C.
 13. A recombinant molecule comprising an ankyrin nucleicacid molecule as set forth in claim 12 operatively linked to atranscription control sequence.
 14. A recombinant virus comprising anankyrin nucleic acid molecule as set forth in claim
 12. 15. Arecombinant cell comprising an ankyrin nucleic acid molecule as setforth in claim
 12. 16. A composition comprising an excipient and anisolated ankyrin nucleic acid molecule wherein said nucleic acidmolecule is a Dirofilaria or Brugia nucleic acid molecule thathybridizes to a nucleic acid molecule having a nucleic acid sequenceselected from the group consisting of SEQ ID NO:86, SEQ ID NO:87, SEQ IDNO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ IDNO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ IDNO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ IDNO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116,SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ IDNO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:143,SEQ ID NO:144 and SEQ ID NO:146 under conditions comprising (a)hybridizing in a solution comprising 2×SSC and 0% formamide, at atemperature of 37° C., and (b) washing in 1×SSC and 0% formamide at atemperature of 49° C.
 17. The composition of claim 16, wherein saidprotective compound is selected from the group consisting of a geneticvaccine, a recombinant virus vaccine and a recombinant cell vaccine. 18.The composition of claim 16, wherein said composition further comprisesa component selected from the group consisting of an adjuvant, acarrier, and a mixture thereof.
 19. A method to produce an ankyrinprotein, said method comprising culturing in an effective medium a cellcapable of expressing said protein, said protein being encoded by aDirofilaria or Brugia nucleic acid molecule that hybridizes to a nucleicacid molecule having a nucleic acid sequence selected from the groupconsisting of SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93,SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103,SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:140, SEQ ID NO:143 and SEQ IDNO:146 under conditions comprising (a) hybridizing in a solutioncomprising 2×SSC and 0% formamide, at a temperature of 37° C., and (b)washing in 1×SSC and 0% formamide at a temperature of 49° C.